ClinicalTrials.gov
ClinicalTrials.gov Menu

Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

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: NCT01339910
Recruitment Status : Terminated (Accrual terminated as recommended by the data and safety monitoring board.)
First Posted : April 21, 2011
Results First Posted : May 30, 2018
Last Update Posted : May 30, 2018
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Information provided by (Responsible Party):
Medical College of Wisconsin

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Myelocytic, Acute
Interventions Drug: Fludarabine and Busulfan
Drug: Fludarabine and Melphalan
Drug: Busulfan and Fludarabine
Drug: Busulfan and Cyclophosphamide
Drug: Cyclophosphamide and Total Body Irradiation
Enrollment 272

Recruitment Details Participants were enrolled between June 2011 and April 2014 from 32 transplant centers
Pre-assignment Details  
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Period Title: Overall Study
Started 135 137
Completed 132 133
Not Completed 3 4
Reason Not Completed
Withdrawal by Subject             1             0
Physician Decision             1             0
Disease relapse             1             4
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC) Total
Hide Arm/Group Description

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Total of all reporting groups
Overall Number of Baseline Participants 135 137 272
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 135 participants 137 participants 272 participants
54.8
(21.9 to 66.0)
54.8
(21.9 to 65.9)
54.8
(21.9 to 66.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Female
59
  43.7%
70
  51.1%
129
  47.4%
Male
76
  56.3%
67
  48.9%
143
  52.6%
Primary Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Acute Myeloid Leukemia (AML)
108
  80.0%
110
  80.3%
218
  80.1%
Myelodysplastic Syndrome (MDS)
27
  20.0%
27
  19.7%
54
  19.9%
MDS WHO Classification   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 27 participants 54 participants
RA/RARS/RCMD/RCMD-RS/Del-5q/MDS-U
16
  59.3%
17
  63.0%
33
  61.1%
RAEB-1
5
  18.5%
5
  18.5%
10
  18.5%
RAEB-2
6
  22.2%
5
  18.5%
11
  20.4%
[1]
Measure Description:

Participants with MDS are categorized per 2008 WHO classification (Vardiman et al. 2009). Major features of each class are given below:

Refractory Anemia (RA): Anemia without marrow blasts or sideroblasts; Refractory Anemia with Ringed Sideroblasts (RARS): > 15% marrow sideroblasts; Refractory Cytopenias with Multilineage Dysplasia (RCMD): Dysplasia in >10% marrow cells; Isolated del(5q) (Del-5q): Isolated del(5q) in marrow; Unclassified (MDS-U) Refractory Anemia with Excess Blasts-1 (RAEB-1): 5-9% marrow blasts; Refractory Anemia with Excess Blasts-2 (RAEB-2): 10-19% marrow blasts;

[2]
Measure Analysis Population Description: Participants with MDS
AML WHO Classification   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 110 participants 218 participants
AML with recurrent genetic abnormalities
12
  11.1%
20
  18.2%
32
  14.7%
AML with multilineage dysplasia
8
   7.4%
12
  10.9%
20
   9.2%
AML and MDS, therapy related
2
   1.9%
3
   2.7%
5
   2.3%
AML, not otherwise specified
86
  79.6%
75
  68.2%
161
  73.9%
[1]
Measure Description:

Participants with AML are categorized per 2008 WHO classification (Vardiman et al. 2009). Major features of each class are given below:

AML with recurrent genetic abnormalities: Presence of specific genetic abnormalities known to be prognostic; AML with multilineage dysplasia: > 50% of cells in at least 2 myeloid lineages are dysplastic; AML and MDS, therapy related: development of myeloid neoplasms in response to therapy that is diagnosed as either AML or MDS; AML not otherwise specified: AML that does not satisfy criteria for other classes

[2]
Measure Analysis Population Description: Participants with AML
Disease Duration  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 135 participants 137 participants 272 participants
6
(2 to 86)
6
(2 to 130)
6
(2 to 130)
Disease Risk Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Standard
74
  54.8%
71
  51.8%
145
  53.3%
High
54
  40.0%
61
  44.5%
115
  42.3%
Unknown
7
   5.2%
5
   3.6%
12
   4.4%
[1]
Measure Description: Disease risk status is defined according to cytogenetic and molecular abnormalities identified prior to transplantation and classified as standard or high risk. Among AML participants, high-risk disease is defined as the presence of cytogenetic abnormalities at 3q, 9q, 11q, 20q, 21q, or 17p; the presence of del(5q)/-5, -7/del(7q), t(6;9), or t(9;22); and/or FLT-3 internal tandem duplication mutation. Among MDS participants, high-risk disease is defined as the presence of > 10% blasts in bone marrow.
HCT-CI   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
0
46
  34.1%
40
  29.2%
86
  31.6%
1-2
45
  33.3%
52
  38.0%
97
  35.7%
3 or more
42
  31.1%
44
  32.1%
86
  31.6%
Unknown
2
   1.5%
1
   0.7%
3
   1.1%
[1]
Measure Description: The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) (Sorror et al., 2005) summarizes relevant comorbidities present in participants prior to allogeneic transplant. Each comorbidity reported at the time of transplant is given a score of 0, 1, 2, or 3 and the overall HCT-CI score is the sum of the comorbidity scores, ranging from 0 - 26.
Conditioning Regimen   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Flu/Bu4
87
  64.4%
0
   0.0%
87
  32.0%
Bu/Cy
40
  29.6%
0
   0.0%
40
  14.7%
Cy/TBI
8
   5.9%
0
   0.0%
8
   2.9%
Flu/Mel
0
   0.0%
27
  19.7%
27
   9.9%
Flu/Bu2
0
   0.0%
110
  80.3%
110
  40.4%
[1]
Measure Description:

Flu/Bu4: busulfan (16 mg/kg oral or 12.8 mg/kg IV) and fludarabine (120-180 mg/m2); Bu/Cy: busulfan (16 mg/kg oral or 12.8 mg/kg IV) and cyclophosphamide (120 mg/kg) ; Cy/TBI: cyclophosphamide (120 mg/kg) and total body irradiation (1200-1420 cGy); Flu/Mel: fludarabine (120-180 mg/m2) and melphalan (≤ 150 mg/m2); Flu/Bu2: fludarabine (120-180 mg/m2) with busulfan (≤ 8 mg/kg oral or 6.4 mg/kg IV);

Flu/Bu4, Bu/Cy, and Cy/TBI are myeloablative conditioning regimens, while Flu/Mel and Flu/Bu2 are reduced intensity conditioning regimens.

GVHD Prophylaxis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Tacrolimus / Methotrexate
110
  81.5%
112
  81.8%
222
  81.6%
Cyclosporine / Methotrexate
3
   2.2%
3
   2.2%
6
   2.2%
TAC / Mycophenolate mofetil
8
   5.9%
5
   3.6%
13
   4.8%
Cyclosporine / Mycophenolate mofetil
1
   0.7%
0
   0.0%
1
   0.4%
Sirolimus / Tacrolimus
10
   7.4%
12
   8.8%
22
   8.1%
Other
3
   2.2%
5
   3.6%
8
   2.9%
[1]
Measure Description: Prophylaxis for Graft Versus Host Disease
ATG Use   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Yes
18
  13.3%
22
  16.1%
40
  14.7%
No
117
  86.7%
115
  83.9%
232
  85.3%
[1]
Measure Description: Use of Anti-Thymocyte Globulin
Donor Type  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Matched Related
57
  42.2%
58
  42.3%
115
  42.3%
Mismatched Related
2
   1.5%
5
   3.6%
7
   2.6%
Matched Unrelated
66
  48.9%
58
  42.3%
124
  45.6%
Mismatched Unrelated
10
   7.4%
16
  11.7%
26
   9.6%
Donor Source  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 137 participants 272 participants
Peripheral Blood
127
  94.1%
123
  89.8%
250
  91.9%
Bone Marrow
8
   5.9%
14
  10.2%
22
   8.1%
1.Primary Outcome
Title Percentage of Participants With Overall Survival (OS)
Hide Description Overall survival is defined as survival of death from any cause.
Time Frame 18 months post-randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage
77.5
(69.4 to 83.7)
67.7
(59.1 to 74.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in overall survival at 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. 18 month overall survival was compared between treatment arms using the difference in Kaplan-Meier estimators, which should be close to 0 under the null hypothesis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments This final test was performed at a 0.049 significance level, since 0.001 was spent at interim analyses and the overall significance level was 0.050.
Method Difference in Kaplan-Meier estimators
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in 18 month OS (MAC-RIC)
Estimated Value 9.8
Confidence Interval (2-Sided) 95%
-0.8 to 20.3
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Relapse-Free Survival (RFS)
Hide Description Relapse-free survival is defined as survival without relapse of the primary disease.
Time Frame 18 months post-randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage
67.8
(59.1 to 75.0)
47.3
(38.7 to 55.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in relapse-free survival at 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. 18 month relapse-free survival was compared between treatment arms using the difference in Kaplan-Meier estimators, which should be close to 0 under the null hypothesis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.01
Comments Test performed at a significance level of 0.05
Method Difference in Kaplan-Meier estimators
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in 18 month RFS (MAC-RIC)
Estimated Value 20.4
Confidence Interval (2-Sided) 95%
8.9 to 32.0
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Disease Relapse
Hide Description Disease Relapse is defined as relapse of the primary disease.
Time Frame 18 months post-randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage
13.5
(8.3 to 19.8)
48.3
(39.6 to 56.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the cumulative incidence of disease relapse during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of disease relapse was compared between treatment arms using Gray's test, treating death as a competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments Test performed at a significance level of 0.05
Method Gray's test
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Treatment-related Mortality
Hide Description Treatment-related mortality is defined as death without a previous relapse of the primary disease.
Time Frame 18 months post-randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 135 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage
15.8
(10.2 to 22.5)
4.4
(1.8 to 8.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the cumulative incidence of treatment-related mortality during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of treatment-related mortality was compared between treatment arms using Gray's test, treating disease relapse as a competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Test performed at a significance level of 0.05
Method Gray's test
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Neutrophil and Platelet Engraftment
Hide Description Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter for 3 consecutive measurements on different days. The first of the 3 days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.
Time Frame Days 28 and 60 post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Number
Unit of Measure: percentage
Neutrophil Engraftment at Day 28 98.5 97.8
Platelet Engraftment at Day 60 95.5 96.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the cumulative incidence of neutrophil engraftment at Day 28 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of neutrophil engraftment at Day 28 was compared between treatment arms using the difference in Aalen-Johansen estimators, which should be close to 0 under the null hypothesis. Death was treated as a competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Test performed at a significance level of 0.05
Method Difference in Aalen-Johansen estimators
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the cumulative incidence of platelet engraftment at Day 60 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of platelet engraftment at Day 60 was compared between treatment arms using the difference in Aalen-Johansen estimators, which should be close to 0 under the null hypothesis. Death was treated as a competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments Test performed at a significance level of 0.05
Method Difference in Aalen-Johansen estimators
Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Donor Cell Engraftment
Hide Description Donor cell engraftment will be assessed by donor-recipient chimerism assays. Full donor chimerism is defined as the presence of at least 95% donor cells as a proportion of the total population in the peripheral blood or bone marrow. Graft rejection is defined as the presence of no more than 5% donor cells as a proportion of the total population. Mixed chimerism is defined as the presence of between 5% and 95% donor cells. Mixed or full donor chimerism will be considered evidence of donor engraftment.
Time Frame Days 28 and 100 and 18 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Count of Participants
Unit of Measure: Participants
Day 28 Full Donor Chimerism
86
  65.2%
80
  60.2%
Mixed Chimerism
9
   6.8%
30
  22.6%
Graft Rejection
1
   0.8%
1
   0.8%
Death Prior to Assessment
0
   0.0%
0
   0.0%
Unknown (relapsed or missing assay)
36
  27.3%
22
  16.5%
Day 100 Full Donor Chimerism
106
  80.3%
86
  64.7%
Mixed Chimerism
12
   9.1%
30
  22.6%
Graft Rejection
2
   1.5%
1
   0.8%
Death Prior to Assessment
6
   4.5%
8
   6.0%
Unknown (relapsed or missing assay)
6
   4.5%
8
   6.0%
18 Months Full Donor Chimerism
71
  53.8%
66
  49.6%
Mixed Chimerism
4
   3.0%
5
   3.8%
Graft Rejection
1
   0.8%
1
   0.8%
Death Prior to Assessment
31
  23.5%
42
  31.6%
Unknown (relapsed or missing assay)
25
  18.9%
19
  14.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the proportions of participants with full chimerism, mixed chimerism, graft rejection, and death prior to assessment at Day 28 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Test performed at a significance level of 0.05
Method Chi-squared
Comments 3 degrees of freedom
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the proportions of participants with full chimerism, mixed chimerism, graft rejection, and death prior to assessment at Day 100 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Test performed at a significance level of 0.05
Method Chi-squared
Comments 3 degrees of freedom
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the proportions of participants with full chimerism, mixed chimerism, graft rejection, and death prior to assessment at 18 months post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments Test performed at a significance level of 0.05
Method Chi-squared
Comments 3 degrees of freedom
7.Secondary Outcome
Title Percentage of Participants With Acute Graft Versus Host Disease (GVHD)
Hide Description

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

Skin stage:

0: No rash

  1. Rash <25% of body surface area
  2. Rash on 25-50% of body surface area
  3. Rash on > 50% of body surface area
  4. Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level)*:

0: <2 mg/dL

  1. 2-3 mg/dL
  2. 3.01-6 mg/dL
  3. 6.01-15.0 mg/dL
  4. >15 mg/dL

GI stage*:

0: No diarrhea or diarrhea <500 mL/day

  1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
  2. Diarrhea 1000-1499 mL/day
  3. Diarrhea >1500 mL/day
  4. Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

GVHD grade:

0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

Time Frame Day 100 post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage
Grade II-IV Acute GVHD
44.7
(36.0 to 53.0)
31.6
(23.8 to 39.6)
Grade III-IV Acute GVHD
13.6
(8.0 to 20.0)
6.8
(3.0 to 12.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the cumulative incidence of grade II-IV acute GVHD during the first 100 days post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of grade II-IV acute GVHD was compared between treatment arms using Gray's test, treating death as a competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments Test performed at a significance level of 0.05
Method Gray's test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the cumulative incidence of grade III-IV acute GVHD during the first 100 days post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of grade III-IV acute GVHD was compared between treatment arms using Gray's test, treating death as a competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments Test performed at a significance level of 0.05
Method Gray's test
Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With Chronic GVHD
Hide Description Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.
Time Frame 18 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage
64.0
(55.0 to 71.7)
47.6
(38.8 to 58.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
Comments The null hypothesis is that there is no difference in the cumulative incidence of chronic GVHD during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of chronic GVHD was compared between treatment arms using Gray's test, treating death as a competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments Test performed at a significance level of 0.05
Method Gray's test
Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants With Chronic GVHD Severity
Hide Description Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.
Time Frame 18 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Count of Participants
Unit of Measure: Participants
None
47
  35.6%
70
  52.6%
Mild
40
  30.3%
34
  25.6%
Moderate
33
  25.0%
17
  12.8%
Severe
12
   9.1%
12
   9.0%
10.Secondary Outcome
Title Number of Participants With Primary Graft Failure
Hide Description Primary graft failure is defined by lack of neutrophil engraftment.
Time Frame 28 days post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.8%
3
   2.3%
11.Secondary Outcome
Title Number of Participants With Secondary Graft Failure
Hide Description Secondary graft failure is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts to less than 500x10^6/liter that is unresponsive to growth factor therapy.
Time Frame 18 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.8%
4
   3.0%
12.Secondary Outcome
Title Number of Participants With Maximum Grade 3-5 Toxicities
Hide Description

The maximum grade of toxicities reported by participants over the study duration are tabulated. Per the CTCAE criteria, toxicities are graded on a scale of 0-5, with higher numbers indicating greater severity. The categories correspond as follows:

3 - severe; 4 - life-threatening; 5 - fatal

Time Frame 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Count of Participants
Unit of Measure: Participants
0-2
34
  25.8%
59
  44.4%
3
66
  50.0%
47
  35.3%
4
22
  16.7%
18
  13.5%
5
10
   7.6%
9
   6.8%
13.Secondary Outcome
Title Infection Type
Hide Description The number and types of infection events reported are tabulated.
Time Frame 18 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Infection events
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Overall Number of Units Analyzed
Type of Units Analyzed: Infection events
353 283
Count of Units
Unit of Measure: Infection events
Bacterial
192
  54.4%
161
  56.9%
Viral
117
  33.1%
95
  33.6%
Fungal
37
  10.5%
12
   4.2%
Protozoal
1
   0.3%
0
   0.0%
Other
6
   1.7%
15
   5.3%
14.Secondary Outcome
Title Number of Participants With Infections
Hide Description

The maximum severity of infections reported by participants are tabulated.

The number of infections and the number of patients experiencing infections will be tabulated by type of infection, severity, and time period after transplant. The cumulative incidence of severe, life-threatening, or fatal infections will be compared between the two treatment arms at 6, 12, and 18 months from transplant or until death.

Time Frame 18 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Transplanted participants
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 132 133
Measure Type: Count of Participants
Unit of Measure: Participants
None
38
  28.8%
43
  32.3%
Moderate
42
  31.8%
37
  27.8%
Severe
40
  30.3%
43
  32.3%
Life Threatening or Fatal
12
   9.1%
10
   7.5%
15.Secondary Outcome
Title Number of Participants With Cause of Death
Hide Description Primary cause of death was adjudicated using previously described criteria (Copelan et al. 2007). When relapse occurred, it was considered the primary cause of death regardless of other events.
Time Frame 18 months post-randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description:

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Overall Number of Participants Analyzed 135 137
Measure Type: Count of Participants
Unit of Measure: Participants
Relapse
10
   7.4%
38
  27.7%
Organ failure
3
   2.2%
1
   0.7%
GVHD
15
  11.1%
4
   2.9%
Infection
2
   1.5%
0
   0.0%
Sudden death
0
   0.0%
1
   0.7%
Still alive
105
  77.8%
93
  67.9%
Time Frame 18 months post-randomization
Adverse Event Reporting Description Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
 
Arm/Group Title Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Hide Arm/Group Description

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
All-Cause Mortality
Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/132 (15.91%)      16/133 (12.03%)    
Blood and lymphatic system disorders     
Autoimmune haemolytic anaemia  1/132 (0.76%)  1 0/133 (0.00%)  0
Immune thrombocytopenic purpura  1/132 (0.76%)  1 0/133 (0.00%)  0
Cardiac disorders     
Acute myocardial infarction  1/132 (0.76%)  1 1/133 (0.75%)  1
Atrial fibrillation  1/132 (0.76%)  1 0/133 (0.00%)  0
Cardiac arrest  0/132 (0.00%)  0 1/133 (0.75%)  1
Pericardial effusion  1/132 (0.76%)  1 1/133 (0.75%)  1
Supraventricular tachycardia  1/132 (0.76%)  1 0/133 (0.00%)  0
Eye disorders     
Vision blurred  1/132 (0.76%)  1 0/133 (0.00%)  0
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1/132 (0.76%)  1 1/133 (0.75%)  1
Oesophagitis  0/132 (0.00%)  0 1/133 (0.75%)  1
Pancreatitis  0/132 (0.00%)  0 1/133 (0.75%)  1
Hepatobiliary disorders     
Hepatic haemorrhage  1/132 (0.76%)  1 0/133 (0.00%)  0
Hyperbilirubinaemia  0/132 (0.00%)  0 1/133 (0.75%)  1
Immune system disorders     
Graft versus host disease  1/132 (0.76%)  1 0/133 (0.00%)  0
Infections and infestations     
Device related infection  1/132 (0.76%)  1 0/133 (0.00%)  0
Enterocolitis infectious  1/132 (0.76%)  1 0/133 (0.00%)  0
Respiratory tract infection  1/132 (0.76%)  1 0/133 (0.00%)  0
Injury, poisoning and procedural complications     
Fall  0/132 (0.00%)  0 1/133 (0.75%)  1
Hip fracture  1/132 (0.76%)  1 0/133 (0.00%)  0
Spinal compression fracture  0/132 (0.00%)  0 1/133 (0.75%)  1
Spinal fracture  0/132 (0.00%)  0 1/133 (0.75%)  1
Investigations     
Blood bilirubin increased  0/132 (0.00%)  0 1/133 (0.75%)  1
Liver function test increased  0/132 (0.00%)  0 1/133 (0.75%)  1
Metabolism and nutrition disorders     
Gout  0/132 (0.00%)  0 1/133 (0.75%)  1
Musculoskeletal and connective tissue disorders     
Back pain  0/132 (0.00%)  0 2/133 (1.50%)  2
Flank pain  1/132 (0.76%)  1 0/133 (0.00%)  0
Nervous system disorders     
Haemorrhage intracranial  1/132 (0.76%)  1 0/133 (0.00%)  0
Posterior reversible encephalopathy syndrome  1/132 (0.76%)  1 0/133 (0.00%)  0
Syncope  2/132 (1.52%)  2 0/133 (0.00%)  0
Vocal cord paralysis  0/132 (0.00%)  0 1/133 (0.75%)  1
Psychiatric disorders     
Mental status changes  1/132 (0.76%)  1 0/133 (0.00%)  0
Renal and urinary disorders     
Hydronephrosis  0/132 (0.00%)  0 1/133 (0.75%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1/132 (0.76%)  1 0/133 (0.00%)  0
Dyspnoea at rest  1/132 (0.76%)  1 0/133 (0.00%)  0
Pulmonary embolism  4/132 (3.03%)  4 1/133 (0.75%)  1
Respiratory distress  0/132 (0.00%)  0 1/133 (0.75%)  1
Respiratory failure  2/132 (1.52%)  2 1/133 (0.75%)  1
Skin and subcutaneous tissue disorders     
Stevens-Johnson syndrome  0/132 (0.00%)  0 1/133 (0.75%)  1
Surgical and medical procedures     
Cholecystectomy  2/132 (1.52%)  2 0/133 (0.00%)  0
Finger amputation  0/132 (0.00%)  0 1/133 (0.75%)  1
Prostatectomy  0/132 (0.00%)  0 1/133 (0.75%)  1
Vascular disorders     
Embolism  1/132 (0.76%)  2 0/133 (0.00%)  0
Hypotension  0/132 (0.00%)  0 2/133 (1.50%)  2
Venoocclusive disease  1/132 (0.76%)  1 0/133 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Myeloablative Conditioning Regimen (MAC) Reduced Intensity Conditioning (RIC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/132 (5.30%)      4/133 (3.01%)    
General disorders     
Chest pain  1/132 (0.76%)  1 0/133 (0.00%)  0
Investigations     
Weight decreased  2/132 (1.52%)  2 1/133 (0.75%)  1
Musculoskeletal and connective tissue disorders     
Arthritis  1/132 (0.76%)  1 0/133 (0.00%)  0
Musculoskeletal pain  1/132 (0.76%)  1 0/133 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Large granular lymphocytosis  1/132 (0.76%)  1 1/133 (0.75%)  1
Nervous system disorders     
Syncope  1/132 (0.76%)  1 0/133 (0.00%)  0
Psychiatric disorders     
Mania  0/132 (0.00%)  0 1/133 (0.75%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1/132 (0.76%)  1 0/133 (0.00%)  0
Surgical and medical procedures     
Hernia repair  0/132 (0.00%)  0 1/133 (0.75%)  1
1
Term from vocabulary, MedDRA 20.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Adam Mendizabal, PhD
Organization: The Emmes Corporation
Phone: 301-251-1161
Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01339910     History of Changes
Other Study ID Numbers: BMTCTN0901
U01HL069294 ( U.S. NIH Grant/Contract )
U01HL069294-05 ( U.S. NIH Grant/Contract )
BMT CTN 0901 ( Other Identifier: Blood and Marrow Transplant Clinical Trial Network )
5U24CA076518 ( U.S. NIH Grant/Contract )
First Submitted: April 20, 2011
First Posted: April 21, 2011
Results First Submitted: March 12, 2018
Results First Posted: May 30, 2018
Last Update Posted: May 30, 2018