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Trial record 80 of 120 for:    stem cell arthritis AND Phase

Scleroderma: Cyclophosphamide or Transplantation (SCOT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00114530
Recruitment Status : Completed
First Posted : June 16, 2005
Results First Posted : July 14, 2017
Last Update Posted : January 29, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Scleroderma, Systemic
Sclerosis
Autoimmune Disease
Interventions Biological: mHSCT
Drug: cyclophosphamide
Enrollment 75
Recruitment Details  
Pre-assignment Details  
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.) Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Period Title: Overall Study
Started 36 39
Completed 27 [1] 19 [1]
Not Completed 9 20
Reason Not Completed
Death             3             11
Lost to Follow-up             1             1
Physician Decision             1             1
Withdrawal by Subject             2             6
Breast Cancer             1             0
Subject decision after endpoint failure             0             1
Ineligible             1             0
[1]
Completed 72 mo, 54 mo after failure, or at least 54 mo at study end (last patient’s 54 mo visit)
Arm/Group Title mHSCT Cyclophosphamide Total
Hide Arm/Group Description Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.) Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2). Total of all reporting groups
Overall Number of Baseline Participants 36 39 75
Hide Baseline Analysis Population Description
Randomized intent to treat
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 39 participants 75 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
35
  97.2%
38
  97.4%
73
  97.3%
>=65 years
1
   2.8%
1
   2.6%
2
   2.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 39 participants 75 participants
44.9  (10.90) 46.9  (10.43) 45.9  (10.63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 39 participants 75 participants
Female
19
  52.8%
29
  74.4%
48
  64.0%
Male
17
  47.2%
10
  25.6%
27
  36.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 39 participants 75 participants
Hispanic or Latino
3
   8.3%
5
  12.8%
8
  10.7%
Not Hispanic or Latino
32
  88.9%
34
  87.2%
66
  88.0%
Unknown or Not Reported
1
   2.8%
0
   0.0%
1
   1.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 39 participants 75 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   5.6%
1
   2.6%
3
   4.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   5.6%
4
  10.3%
6
   8.0%
White
29
  80.6%
31
  79.5%
60
  80.0%
More than one race
2
   5.6%
3
   7.7%
5
   6.7%
Unknown or Not Reported
1
   2.8%
0
   0.0%
1
   1.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 39 participants 75 participants
Canada 1 2 3
United States 35 37 72
Health Assessment Questionnaire - Disability Index (HAQ-DI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 36 participants 39 participants 75 participants
1.2  (0.65) 1.4  (0.86) 1.3  (0.77)
[1]
Measure Description: HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome.
Short Form 36 Health Survey (SF-36)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 36 participants 39 participants 75 participants
Physical Component Score 29.5  (9.20) 28.9  (9.46) 29.2  (9.27)
Mental Component Score 44.7  (10.70) 44.6  (9.86) 44.6  (10.21)
[1]
Measure Description: The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component was transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population.
Diffusion in Liters of Carbon Monoxide (DLCO) (Percent-Predicted)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent predicted
Number Analyzed 36 participants 39 participants 75 participants
53.9  (7.63) 52.7  (8.19) 53.3  (7.90)
[1]
Measure Description: Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations and adjusted per the Cotes formula for anemia, if a participant’s hemoglobin was <13 or >17 gm/dL, and altitude (Calgary site only).
Forced Vital Capacity (FVC) (Percent-Predicted)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent predicted
Number Analyzed 36 participants 39 participants 75 participants
74.5  (14.77) 73.8  (16.98) 74.2  (15.86)
[1]
Measure Description: Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards.
Modified Rodnan Skin Score (mRSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 36 participants 39 participants 75 participants
28.5  (8.72) 30.8  (10.55) 29.7  (9.72)
[1]
Measure Description: The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity.
Disease-Modifying Anti-Rheumatic Drug (DMARD) Use Within 6 Months of Randomization   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 39 participants 75 participants
26
  72.2%
25
  64.1%
51
  68.0%
[1]
Measure Description: Use of any disease-modifying antirheumatic drugs (DMARDs) within six months prior to randomization. DMARDS can include, but are not limited to, methotrexate, cyclophosphamide, azathioprine, leflunomide, mycophenolate mofetil, D-penicillamine, tacrolimus, cyclosporine, prednisone >10 mg, and TNF-blockers.
Disease-Modifying Anti-Rheumatic Drug (DMARD) Use   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 39 participants 75 participants
27
  75.0%
32
  82.1%
59
  78.7%
[1]
Measure Description: Any use of disease-modifying antirheumatic drugs (DMARDs) prior to randomization. DMARDS can include, but are not limited to, methotrexate, cyclophosphamide, azathioprine, leflunomide, mycophenolate mofetil, D-penicillamine, tacrolimus, cyclosporine, prednisone >10 mg, and TNF-blockers.
1.Primary Outcome
Title Global Rank Composite Score (GRCS) (Month 54, ITT)
Hide Description The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of >30% in DLCO % predicted or >20% in FVC % predicted ), renal failure (chronic dialysis > 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction <30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Median (Full Range)
Unit of Measure: Sum of subject-pair comparison scores
17.0
(-58 to 52)
-6.0
(-58 to 52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments A Data and Safety Monitoring Board reviewed 4 pre-specified futility analyses that included an ability to stop for efficacy with p<0.0001, leaving alpha equal to 0.0496 for the primary ITT analysis of the GRCS at 54 months post-randomization.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Global Rank Composite Score (GRCS) (Month 54, PP)
Hide Description The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of >30% in DLCO % predicted or >20% in FVC % predicted ), renal failure (chronic dialysis > 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction <30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Median (Full Range)
Unit of Measure: Sum of subject-pair comparison scores
16
(-56 to 46)
-11.0
(-56 to 46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Global Rank Composite Score (GRCS) (Month 48, ITT)
Hide Description The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of >30% in DLCO % predicted or >20% in FVC % predicted ), renal failure (chronic dialysis > 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction <30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Median (Full Range)
Unit of Measure: Sum of subject-pair comparison scores
20.0
(-58 to 55)
-8.0
(-58 to 55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Global Rank Composite Score (GRCS) (Month 48, PP)
Hide Description The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of >30% in DLCO % predicted or >20% in FVC % predicted ), renal failure (chronic dialysis > 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction <30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Median (Full Range)
Unit of Measure: Sum of subject-pair comparison scores
17.0
(-56 to 49)
-13.0
(-56 to 49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Event-Free Survival (EFS) (Month 54, ITT)
Hide Description Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of >30% in diffusion in liters of carbon monoxide (DLCO) % predicted or >20% in forced vital capacity (FVC) % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis > 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction <30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 54 post-randomization.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
EFS Failure
10
  27.8%
20
  51.3%
Survived Event Free
26
  72.2%
19
  48.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Treatment arm comparisons of EFS at Month 54.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Treatment arm comparisons of Kaplan-Meier curves for EFS through Month 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.06
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
6.Secondary Outcome
Title Event-Free Survival (EFS) (Month 54, PP)
Hide Description Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of >30% in DLCO % predicted or >20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis > 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction <30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 54 post-randomization.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
EFS Failure
7
  21.2%
17
  50.0%
Survived Event Free
26
  78.8%
17
  50.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Treatment arm comparisons of EFS at Month 54.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Treatment arm comparisons of Kaplan-Meier curves for EFS through Month 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Event-Free Survival (EFS) (Month 48, ITT)
Hide Description Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of >30% in DLCO % predicted or >20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis > 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction <30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 48 post-randomization.
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
EFS Failure
10
  27.8%
20
  51.3%
Survived Event Free
26
  72.2%
19
  48.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
8.Secondary Outcome
Title Event-Free Survival (EFS) (Month 48, PP)
Hide Description Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of >30% in DLCO % predicted or >20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis > 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction <30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 48 post-randomization.
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
EFS Failure
7
  21.2%
17
  50.0%
Survived Event Free
26
  78.8%
17
  50.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Secondary Outcome
Title Treatment-Related Mortality (Month 54, ITT)
Hide Description Death, occurring at any time between randomization and Month 54 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
1
   2.8%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
10.Secondary Outcome
Title Treatment-Related Mortality (Month 54, PP)
Hide Description Death, occurring at any time between randomization and Month 54 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
11.Secondary Outcome
Title Treatment-Related Mortality (Month 48, ITT)
Hide Description Death, occurring at any time between randomization and Month 48 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
1
   2.8%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
12.Secondary Outcome
Title Treatment-Related Mortality (Month 48, PP)
Hide Description Death, occurring at any time between randomization and Month 48 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
13.Secondary Outcome
Title All-Cause Mortality (Month 54, ITT)
Hide Description Any death, regardless of relationship to treatment, between randomization and Month 54 post-randomization.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
6
  16.7%
11
  28.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Treatment arm comparisons of overall survival at Month 54.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Treatment arm comparisons of Kaplan-Meier curves for overall survival through Month 72.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
14.Secondary Outcome
Title All-Cause Mortality (Month 54, PP)
Hide Description Any death, regardless of relationship to treatment, between randomization and Month 54 post-randomization.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
3
   9.1%
8
  23.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT
Comments Treatment arm comparisons of overall survival at Month 54.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Treatment arm comparisons of Kaplan-Meier curves for overall survival through Month 72.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
15.Secondary Outcome
Title All-Cause Mortality (Month 48, ITT)
Hide Description Any death, regardless of relationship to treatment, between randomization and Month 48 post-randomization.
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
6
  16.7%
11
  28.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
16.Secondary Outcome
Title All-Cause Mortality (Month 48, PP)
Hide Description Any death, regardless of relationship to treatment, between randomization and Month 48 post-randomization.
Time Frame 48 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
3
   9.1%
8
  23.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (ITT)
Hide Description HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome. Analysis was based on an ordinal response variable, defined as follows: a decrease of >0.4 from baseline in the HAQ-DI score was considered disease improvement, an increase of >0.4 was considered disease worsening, and any change less than 0.4 was considered “no change.” Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 19 10 20
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
17
  65.4%
6
  31.6%
2
  20.0%
0
   0.0%
No Change
8
  30.8%
11
  57.9%
5
  50.0%
11
  55.0%
Worsening
1
   3.8%
2
  10.5%
3
  30.0%
9
  45.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
18.Secondary Outcome
Title Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (PP)
Hide Description HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome. Analysis was based on an ordinal response variable, defined as follows: a decrease of >0.4 from baseline in the HAQ-DI score was considered disease improvement, an increase of >0.4 was considered disease worsening, and any change less than 0.4 was considered “no change.” Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 17 7 17
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
17
  65.4%
6
  35.3%
2
  28.6%
0
   0.0%
No Change
8
  30.8%
10
  58.8%
5
  71.4%
9
  52.9%
Worsening
1
   3.8%
1
   5.9%
0
   0.0%
8
  47.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
19.Secondary Outcome
Title Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT)
Hide Description The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component was transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population. Analysis was based on ordinal response, defined as follows for each component: a >= 10 point increase indicated disease improvement, a >= 10 point decrease indicated disease worsening, and a change <10 points indicated “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 19 10 20
Measure Type: Count of Participants
Unit of Measure: Participants
Physical Component Score: Improvement
19
  73.1%
6
  31.6%
1
  10.0%
0
   0.0%
Physical Component Score: No Change
6
  23.1%
9
  47.4%
6
  60.0%
16
  80.0%
Physical Component Score: Worsening
1
   3.8%
4
  21.1%
3
  30.0%
4
  20.0%
Mental Component Score: Improvement
10
  38.5%
2
  10.5%
1
  10.0%
1
   5.0%
Mental Component Score: No Change
12
  46.2%
12
  63.2%
5
  50.0%
12
  60.0%
Mental Component Score: Worsening
4
  15.4%
5
  26.3%
4
  40.0%
7
  35.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Physical Component Score. This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Physical Component Score. This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Mental Component Score. This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Mental Component Score. This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
20.Secondary Outcome
Title Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP)
Hide Description The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component was transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population. Analysis was based on ordinal response, defined as follows for each component: a >= 10 point increase indicated disease improvement, a >= 10 point decrease indicated disease worsening, and a change <10 points indicated “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 17 7 17
Measure Type: Count of Participants
Unit of Measure: Participants
Physical Component Score: Improvement
19
  73.1%
6
  35.3%
1
  14.3%
0
   0.0%
Physical Component Score: No Change
6
  23.1%
9
  52.9%
6
  85.7%
14
  82.4%
Physical Component Score: Worsening
1
   3.8%
2
  11.8%
0
   0.0%
3
  17.6%
Mental Component Score: Improvement
10
  38.5%
2
  11.8%
1
  14.3%
1
   5.9%
Mental Component Score: No Change
12
  46.2%
12
  70.6%
5
  71.4%
10
  58.8%
Mental Component Score: Worsening
4
  15.4%
3
  17.6%
1
  14.3%
6
  35.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Physical Component Score. This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Physical Component Score. This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Mental Component Score. This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments Mental Component Score. This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
21.Secondary Outcome
Title Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (ITT)
Hide Description Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations and adjusted per the Cotes formula for anemia, if a participant’s hemoglobin was <13 or >17 gm/dL, and altitude (Calgary site only). Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of >15% in DLCO % Predicted indicated disease improvement, a decrease of >15% indicated disease worsening, and a change of <=15% was considered “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 19 10 20
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
4
  15.4%
5
  26.3%
0
   0.0%
0
   0.0%
No Change
19
  73.1%
8
  42.1%
0
   0.0%
2
  10.0%
Worsening
3
  11.5%
6
  31.6%
10
 100.0%
18
  90.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
22.Secondary Outcome
Title Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (PP)
Hide Description Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations and adjusted per the Cotes formula for anemia, if a participant’s hemoglobin was <13 or >17 gm/dL, and altitude (Calgary site only). Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of >15% in DLCO % Predicted indicated disease improvement, a decrease of >15% indicated disease worsening, and a change of <=15% was considered “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 17 7 17
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
4
  15.4%
5
  29.4%
0
   0.0%
0
   0.0%
No Change
19
  73.1%
8
  47.1%
0
   0.0%
2
  11.8%
Worsening
3
  11.5%
4
  23.5%
7
 100.0%
15
  88.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
23.Secondary Outcome
Title Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (ITT)
Hide Description Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards. Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of >10% in FVC % Predicted indicated disease improvement, a decrease of >10% indicated disease worsening, and a change of <=10% was considered “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 19 10 20
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
12
  46.2%
7
  36.8%
0
   0.0%
1
   5.0%
No Change
13
  50.0%
8
  42.1%
2
  20.0%
2
  10.0%
Worsening
1
   3.8%
4
  21.1%
8
  80.0%
17
  85.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
24.Secondary Outcome
Title Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (PP)
Hide Description Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards. Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of >10% in FVC % Predicted indicated disease improvement, a decrease of >10% indicated disease worsening, and a change of <=10% was considered “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 17 7 17
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
12
  46.2%
7
  41.2%
0
   0.0%
1
   5.9%
No Change
13
  50.0%
8
  47.1%
2
  28.6%
2
  11.8%
Worsening
1
   3.8%
2
  11.8%
5
  71.4%
14
  82.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
25.Secondary Outcome
Title Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (ITT)
Hide Description The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity. Analysis was based on an ordinal response variable, defined as follows: if the baseline mRSS was <=20, a decrease >=5 points from baseline indicated disease improvement and an increase >= 5 points indicated disease worsening; if the baseline mRSS was >20, then a decrease of >25% indicated disease improvement and an increase of >25% indicated disease worsening. Participants who do not meet the disease criteria outlined above were considered “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 19 10 20
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
26
 100.0%
14
  73.7%
5
  50.0%
5
  25.0%
No Change
0
   0.0%
3
  15.8%
1
  10.0%
10
  50.0%
Worsening
0
   0.0%
2
  10.5%
4
  40.0%
5
  25.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
26.Secondary Outcome
Title Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (PP)
Hide Description The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity. Analysis was based on an ordinal response variable, defined as follows: if the baseline mRSS was <=20, a decrease >=5 points from baseline indicated disease improvement and an increase >= 5 points indicated disease worsening; if the baseline mRSS was >20, then a decrease of >25% indicated disease improvement and an increase of >25% indicated disease worsening. Participants who do not meet the disease criteria outlined above were considered “no change”. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT- EFS Survivor Cyclophosphamide-EFS Survivor mHSCT- EFS Failure Cyclophosphamide- EFS Failure
Hide Arm/Group Description:
Subjects in the mHSCT group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who met the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Overall Number of Participants Analyzed 26 17 7 17
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement
26
 100.0%
14
  82.4%
5
  71.4%
5
  29.4%
No Change
0
   0.0%
3
  17.6%
1
  14.3%
10
  58.8%
Worsening
0
   0.0%
0
   0.0%
1
  14.3%
2
  11.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is not stratified. EFS survivors and failures are pooled within each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments Computed as Mantel Haenszel Chi Square using modified ridit scores.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT- EFS Survivor, Cyclophosphamide-EFS Survivor, mHSCT- EFS Failure, Cyclophosphamide- EFS Failure
Comments This analysis is stratified by EFS status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Van Elteren extension of the Wilcoxon Rank Sum
27.Secondary Outcome
Title New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (ITT)
Hide Description Any events that met the criteria outlined below or were reported as adverse events between randomization and Month 54 post-randomization are summarized. 1) Development of new or worsening arrhythmias that require medical treatment for >= 3 months or require ablative therapy or pacemaker insertion. (Note that for a participant who has medically controlled arrhythmia at randomization, worsening was defined as breakthrough episodes severe enough to prompt change in medication, an increase in the dose of a medication, or addition of a new medication to maintain control of the arrhythmia.) 2) Congestive heart failure (CHF) requiring clinical treatment for >= 3 months develops. 3) Clinically significant pericardial effusion (excess fluid around the heart) that required pericardial window.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
Development of new or worsening arrhythmias
6
  16.7%
4
  10.3%
CHF requiring clinical treatment
0
   0.0%
4
  10.3%
Clinically significant pericardial effusion
2
   5.6%
1
   2.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Development of new or worsening arrhythmias
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments CHF requiring clinical treatment
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Clinically significant pericardial effusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
28.Secondary Outcome
Title New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (PP)
Hide Description Any events that met the criteria outlined below or were reported as adverse events between randomization and Month 54 post-randomization are summarized. 1) Development of new or worsening arrhythmias that require medical treatment for >= 3 months or require ablative therapy or pacemaker insertion. (Note that for a participant who has medically controlled arrhythmia at randomization, worsening will be defined as breakthrough episodes severe enough to prompt change in medication, an increase in the dose of a medication or addition of a new medication to maintain control of the arrhythmia.) 2) Congestive heart failure (CHF) requiring clinical treatment for >= 3 months develops. 3) Clinically significant pericardial effusion (excess fluid around the heart) that required pericardial window.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
Development of new or worsening arrhythmias
6
  18.2%
4
  11.8%
CHF requiring clinical treatment
0
   0.0%
4
  11.8%
Clinically significant pericardial effusion
2
   6.1%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Development of new or worsening arrhythmias
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments CHF requiring clinical treatment
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments Clinically significant pericardial effusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
29.Secondary Outcome
Title New or Worsening Pulmonary Hypertension (ITT)
Hide Description Any pulmonary arterial hypertension (PAH) events that occurred between randomization and Month 54 post-randomization were summarized. Development of PAH occurred if the participant met the following criteria, where the measurement value(s) could not be explained by other causes such as congestive heart failure or pulmonary emboli: 1) a post-baseline peak systolic pulmonary artery pressure > 55 mmHg by echocardiogram or 2) a mean pulmonary artery pressure > 30 mmHg at rest measured by right heart catheterization. If the post-baseline peak systolic pulmonary artery pressure was between 40 to 55 mmHg by echocardiogram, a right heart catheterization was done to confirm a diagnosis of pulmonary artery hypertension. The endpoint was met if the mean pulmonary artery pressure was > 30 mmHg at rest by right heart catheterization. Additionally, any adverse event reported as PAH was included in the analysis.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
5
  12.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
30.Secondary Outcome
Title New or Worsening Pulmonary Hypertension (PP)
Hide Description Any pulmonary arterial hypertension (PAH) events that occurred between randomization and Month 54 post-randomization were summarized. Development of PAH occurred if the participant met the following criteria, where the measurement value(s) could not be explained by other causes such as congestive heart failure or pulmonary emboli: 1) a post-baseline peak systolic pulmonary artery pressure > 55 mmHg by echocardiogram or 2) a mean pulmonary artery pressure > 30 mmHg at rest measured by right heart catheterization. If the post-baseline peak systolic pulmonary artery pressure was between 40 to 55 mmHg by echocardiogram, a right heart catheterization would be done to confirm a diagnosis of pulmonary artery hypertension. The endpoint was met if the mean pulmonary artery pressure was > 30 mmHg at rest by right heart catheterization. Additionally, any adverse event reported as PAH was included in the analysis.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
5
  14.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
31.Secondary Outcome
Title Occurrence of Scleroderma Renal Crisis (ITT)
Hide Description Documented scleroderma renal crisis (hypertensive or non-hypertensive) occurring from randomization to Month 54 post-randomization was summarized. A hypertensive scleroderma renal crisis occurred if a participant obtained both of the following: New-onset hypertension, defined as systolic blood pressure (SBP) >= 140 mmHg, diastolic blood pressure (DBP) >= 90 mmHg, a rise in SBP >= 30 mmHg compared to baseline, or a rise in DBP >= 20 mmHg compared to baseline, and one of the following features: 1) increase of >= 50 % above baseline in serum creatinine, 2) proteinuria (>= 2+ by dipstick confirmed by protein:creatinine ratio > 2.5), 3) hematuria (>= 2+ by dipstick or > 10 RBCs/HPF, without menstruation), 4) thrombocytopenia (< 100,000 plts/mm3), or 5) hemolysis (determined by blood smear or increased reticulocyte count). Additionally, any adverse event reported as a scleroderma renal crisis was included in the analysis.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.6%
3
   7.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
32.Secondary Outcome
Title Occurrence of Scleroderma Renal Crisis (PP)
Hide Description Documented scleroderma renal crisis (hypertensive or non-hypertensive) occurring from randomization to Month 54 post-randomization was summarized. A hypertensive scleroderma renal crisis occurred if a participant obtained both of the following: New-onset hypertension, defined as systolic blood pressure (SBP) >= 140 mmHg, diastolic blood pressure (DBP) >= 90 mmHg, a rise in SBP >= 30 mmHg compared to baseline, or a rise in DBP >= 20 mmHg compared to baseline, and one of the following features: 1) increase of >= 50 % above baseline in serum creatinine, 2) proteinuria (>= 2+ by dipstick confirmed by protein:creatinine ratio > 2.5), 3) hematuria (>= 2+ by dipstick or > 10 RBCs/HPF, without menstruation), 4) thrombocytopenia (< 100,000 plts/mm3), or 5) hemolysis (determined by blood smear or increased reticulocyte count). Additionally, any adverse event reported as a scleroderma renal crisis was included in the analysis.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   2.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
33.Secondary Outcome
Title Documented Myositis (ITT)
Hide Description Number of participants who experienced any event of myositis that occurred from randomization to Month 54 post-randomization. Documented myositis occurred if the participant had 1) elevated creatine phosphokinase (CPK), electromyography, and/or biopsy and 2) required > 30 mg per day prednisone for over 1 month or another therapy such as methotrexate (MTX) for treatment of myositis. Additionally, any adverse event reported as myositis was included in the analysis.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
1
   2.8%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
34.Secondary Outcome
Title Documented Myositis (PP)
Hide Description Number of participants who experienced any event of myositis that occurred from randomization to Month 54 post-randomization. Documented myositis occurred if the participant had 1) elevated creatine phosphokinase (CPK), electromyography, and/or biopsy and 2) required > 30 mg per day prednisone for over 1 month or another therapy such as methotrexate (MTX) for treatment of myositis. Additionally, any adverse event reported as myositis was included in the analysis.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
35.Secondary Outcome
Title Initiating Use of Disease-Modifying Antirheumatic Drugs (DMARDs) by Month 54 (ITT)
Hide Description Initiation of disease-modifying antirheumatic drugs (DMARDs). Participants were not expected to receive additional disease-modifying therapy for systemic sclerosis (SSc) in the absence of disease progression. In general, this includes the administration of any therapy clearly given for the purpose of treating the underlying SSc. It does not include concomitant treatments permitted in the protocol, such as use of methotrexate (15 g or less), anti-malarials, or minocycline for arthritis only. Systemic corticosteroids given at > 10 mg/day (prednisone or prednisone equivalent), without clearly defined non-SSc indications, and methotrexate given for non-arthritis indications are examples of qualifying DMARDs.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). The ITT population includes all randomized participants.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 36 39
Measure Type: Count of Participants
Unit of Measure: Participants
3
   8.3%
15
  38.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
36.Secondary Outcome
Title Initiating Use of Disease-Modifying Antirheumatic Drugs by Month 54 (DMARDs) (PP)
Hide Description Initiation of disease-modifying antirheumatic drugs (DMARDs). Participants were not expected to receive additional disease-modifying therapy for systemic sclerosis (SSc) in the absence of disease progression. In general, this includes the administration of any therapy clearly given for the purpose of treating the underlying SSc. It does not include concomitant treatments permitted in the protocol, such as use of methotrexate (15 g or less), anti-malarials, or minocycline for arthritis only. Systemic corticosteroids given at > 10 mg/day (prednisone or prednisone equivalent), without clearly defined non-SSc indications, and methotrexate given for non-arthritis indications are examples of qualifying DMARDs.
Time Frame 54 Months Post-Randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 33 34
Measure Type: Count of Participants
Unit of Measure: Participants
3
   9.1%
15
  44.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
37.Secondary Outcome
Title Regimen-Related Toxicities
Hide Description Regimen-related toxicities are defined as Grade 3 or higher adverse events reported by site physicians as possibly, probably, or definitely related to study therapy.
Time Frame Randomization through end of study follow-up (up to Month 72 post-randomization)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 34 37
Measure Type: Number
Unit of Measure: Events
Possibly Related 106 23
Probably Related 98 13
Definitely Related 90 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Linear
Comments P-value comes from a Poisson regression comparing the person-year adjusted event rates between the two treatment groups.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Person-Time (Years)
Estimated Value 174.4
Estimation Comments The Person-Time (P-T) rates (events/P-T) are as follows: Possibly related = 0.61, Probably related = 0.57, Definitely related = 0.52
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Person-Time (Years)
Estimated Value 141.3
Estimation Comments The Person-Time (P-T) rates (events/P-T) are as follows: Possibly related = 0.17, Probably related = 0.09, Definitely related = 0.04
38.Secondary Outcome
Title Number of Subjects With Regimen-Related Toxicities
Hide Description Regimen-related toxicities are defined as Grade 3 or higher adverse events reported by site physicians as possibly, probably, or definitely related to study therapy.
Time Frame Randomization through end of study follow-up (up to Month 72 post-randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 34 37
Measure Type: Count of Participants
Unit of Measure: Participants
Possibly Related
33
  97.1%
10
  27.0%
Probably Related
27
  79.4%
10
  27.0%
Definitely Related
26
  76.5%
3
   8.1%
39.Secondary Outcome
Title Infectious Complications
Hide Description Infectious complications include any events that code to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class of “Infections and infestations” or events that a site has classified as an infectious event. These can include bacteremia, septicemia, fungemia, fever associated with infection, infectious pneumonia, idiopathic pneumonia syndrome, clinical infection (i.e. infection diagnosed with clinical features without identification of an organism) and other local/organ site-specific infections.
Time Frame Randomization through end of study follow-up (up to Month 72 post-randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 34 37
Measure Type: Number
Unit of Measure: Events
131 112
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mHSCT, Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7
Comments [Not Specified]
Method Regression, Linear
Comments P-value comes from a Poisson regression comparing the person-year adjusted event rates between the two treatment groups.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection mHSCT
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Person-Time (Years)
Estimated Value 174.4
Estimation Comments The Person-Time (P-T) rate (events/P-T) is 0.76
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cyclophosphamide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Person-Time (Years)
Estimated Value 141.3
Estimation Comments The Person-Time (P-T) rate (events/P-T) is 0.80
40.Secondary Outcome
Title Number of Subjects With Infectious Complications
Hide Description Infectious complications include any events that code to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class of “Infections and infestations” or events that a site has classified as an infectious event. These can include bacteremia, septicemia, fungemia, fever associated with infection, infectious pneumonia, idiopathic pneumonia syndrome, clinical infection (i.e. infection diagnosed with clinical features without identification of an organism) and other local/organ site-specific infections.
Time Frame Randomization through end of study follow-up (up to Month 72 post-randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Overall Number of Participants Analyzed 34 37
Measure Type: Count of Participants
Unit of Measure: Participants
33
  97.1%
31
  83.8%
41.Secondary Outcome
Title Time to Absolute Neutrophil Count Engraftment
Hide Description Time to absolute neutrophil count (ANC) engraftment is defined as the number of days post-transplant until required levels of ANC are attained (for the mHSCT arm only). If engraftment did not occur within 28 days post-transplant, then the variable was set to 28 days. ANC engraftment required an ANC of > 500 cells/microliter, maintained for 3 consecutive days.
Time Frame 28 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol (PP) – mHSCT arm only. The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm.
Arm/Group Title mHSCT
Hide Arm/Group Description:
Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Overall Number of Participants Analyzed 34
Median (Full Range)
Unit of Measure: Days
10
(8 to 12)
Time Frame From randomization until study completion, an average of 72 months, or until 30 days after a participant withdrew early from the study.
Adverse Event Reporting Description Adverse events were collected in the safety population, which includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment began with the first dose of granulocyte colony stimulating factor for mobilization; for the cyclophosphamide arm, treatment began with the first dose of IV cyclophosphamide. In the mHSCT arm, Grade 4 cytopenias reported in participants that occur between conditioning and Day 28 after infusion of the IP, are not reported as SAEs.
 
Arm/Group Title mHSCT Cyclophosphamide
Hide Arm/Group Description Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.) Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
All-Cause Mortality
mHSCT Cyclophosphamide
Affected / at Risk (%) Affected / at Risk (%)
Total   5/34 (14.71%)      13/37 (35.14%)    
Show Serious Adverse Events Hide Serious Adverse Events
mHSCT Cyclophosphamide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/34 (73.53%)      19/37 (51.35%)    
Blood and lymphatic system disorders     
Anaemia  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Febrile neutropenia  1  2/34 (5.88%)  2 1/37 (2.70%)  1
Leukopenia  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Lymphopenia  1  4/34 (11.76%)  6 3/37 (8.11%)  3
Neutropenia  1  2/34 (5.88%)  2 2/37 (5.41%)  2
Cardiac disorders     
Arrhythmia  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Atrial fibrillation  1  0/34 (0.00%)  0 2/37 (5.41%)  2
Atrial flutter  1  1/34 (2.94%)  2 0/37 (0.00%)  0
Cardiac failure congestive  1  0/34 (0.00%)  0 3/37 (8.11%)  4
Left ventricular failure  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Myocardial infarction  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Pericardial effusion  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  1/34 (2.94%)  1 1/37 (2.70%)  1
Colonic obstruction  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Diarrhoea  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Faecaloma  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Gastric antral vascular ectasia  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Gastrointestinal haemorrhage  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Ileus  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Intestinal hypomotility  1  1/34 (2.94%)  1 2/37 (5.41%)  2
Nausea  1  1/34 (2.94%)  1 1/37 (2.70%)  1
Pancreatitis  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Pneumatosis cystoides intestinalis  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Pneumoperitoneum  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Small intestinal obstruction  1  1/34 (2.94%)  4 1/37 (2.70%)  1
General disorders     
Chest pain  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Heparin-induced thrombocytopenia  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Pyrexia  1  2/34 (5.88%)  2 0/37 (0.00%)  0
Hepatobiliary disorders     
Cholelithiasis  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Immune system disorders     
Graft versus host disease  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Hypersensitivity  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Infections and infestations     
Bacteraemia  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Bronchitis viral  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Cellulitis  1  1/34 (2.94%)  1 1/37 (2.70%)  2
Cellulitis staphylococcal  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Fungaemia  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Herpes zoster  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Meningitis enterococcal  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Pneumonia  1  5/34 (14.71%)  6 1/37 (2.70%)  1
Sepsis  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Septic shock  1  1/34 (2.94%)  1 1/37 (2.70%)  1
Staphylococcal infection  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Urinary tract infection  1  0/34 (0.00%)  0 2/37 (5.41%)  4
Viral infection  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Injury, poisoning and procedural complications     
Femoral neck fracture  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Investigations     
Pulmonary function test decreased  1  1/34 (2.94%)  1 4/37 (10.81%)  5
Metabolism and nutrition disorders     
Failure to thrive  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Fluid retention  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Hypokalaemia  1  0/34 (0.00%)  0 1/37 (2.70%)  2
Musculoskeletal and connective tissue disorders     
Bone pain  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Myositis  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Scleroderma  1  0/34 (0.00%)  0 2/37 (5.41%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Breast cancer recurrent  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Myelodysplastic syndrome  1  2/34 (5.88%)  2 0/37 (0.00%)  0
Papillary thyroid cancer  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Nervous system disorders     
Carotid artery stenosis  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Dizziness  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Dystonia  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Psychiatric disorders     
Depression  1  1/34 (2.94%)  1 1/37 (2.70%)  1
Major depression  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Renal and urinary disorders     
Renal failure  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Scleroderma renal crisis  1  1/34 (2.94%)  1 3/37 (8.11%)  5
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Aspiration  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Capillary leak syndrome  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Dyspnoea  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Hypoxia  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Interstitial lung disease  1  1/34 (2.94%)  1 1/37 (2.70%)  1
Pneumonia aspiration  1  1/34 (2.94%)  1 1/37 (2.70%)  2
Pneumonitis  1  3/34 (8.82%)  3 0/37 (0.00%)  0
Pulmonary alveolar haemorrhage  1  1/34 (2.94%)  1 0/37 (0.00%)  0
Pulmonary embolism  1  0/34 (0.00%)  0 1/37 (2.70%)  1
Pulmonary hypertension  1  0/34 (0.00%)