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5-Azacytidine Prior to Allogeneic Stem Cell Transplant in High Risk Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT00721214
Recruitment Status : Completed
First Posted : July 24, 2008
Results First Posted : August 3, 2015
Last Update Posted : March 2, 2016
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Virginia Commonwealth University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Myelodysplastic Syndrome
Intervention Drug: 5-azacytidine
Enrollment 16
Recruitment Details This study plans to accrue over one year with a planned 2 year subsequent follow-up. Virginia Commonwealth Unvierstiy (VCU) will be the sole site for this project.
Pre-assignment Details  
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Period Title: Overall Study
Started 16
Completed 12
Not Completed 4
Reason Not Completed
Chose another center for transplant             1
Death             3
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
Out of the 16 evaluable patients, 12 were able to proceed to transplant.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
  93.8%
>=65 years
1
   6.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
54  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
10
  62.5%
Male
6
  37.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants
16
1.Primary Outcome
Title One Year Overall Survival of Allogeneic Transplant Recipients After Transplantation
Hide Description Percentage of patients alive one year after their transplantation, as estimated by the Kaplan-Meier survival curve. The estimated one year survival rate from this curve is 50%, while the estimated two year survival rate is 50%.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(20 to 80)
2.Primary Outcome
Title Two Year Overall Survival of Allogeneic Transplant Recipients After Transplantation
Hide Description Percentage of patients alive two years after their transplantation, as estimated by the Kaplan-Meier survival curve. The estimated two year survival rate is 50%, the same as one year survival rate.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(20 to 80)
3.Primary Outcome
Title One Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation
Hide Description Percentage of participants that received allogeneic transplant and had event free survival, as estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. The estimated one-year event-free survival rate is the same as overall survival, 50%.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(20 to 80)
4.Primary Outcome
Title Two Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation
Hide Description Percentage of participants that received allogeneic transplant and had event free survival. The percentage of patients was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. The estimated two-year event-free survival rate is the same as overall survival, 50%.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(20 to 80)
5.Secondary Outcome
Title One-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts
Hide Description Percentage of participants alive one year after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored. The estimated one year overall survival rate from this curve is 47%. The one year overall survival is the same as one year event free survival rate.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47
(20 to 74)
6.Secondary Outcome
Title Two-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts.
Hide Description Percentage of participants alive two years after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated two year survival rate is 37% .The estimated two-year overall survival rate is the same as two-year event free survival.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
37
(9 to 65)
7.Secondary Outcome
Title One-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts
Hide Description Percentage of participants with one year event free survival after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated one-year event-free survival rate is the same as for overall survival, 47% (SE = 13.6%).
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47
(20 to 74)
8.Secondary Outcome
Title Two-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts
Hide Description Percentage of participants with two year event free survival after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated two- year event-free survival rate is the same as for overall survival, 37% (SE = 14.3%).
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description:

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

Overall Number of Participants Analyzed 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
37
(9 to 65)
Time Frame 3 years
Adverse Event Reporting Description Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
 
Arm/Group Title Arm A: 5-azacytidine
Hide Arm/Group Description

5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.

5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.

All-Cause Mortality
Arm A: 5-azacytidine
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm A: 5-azacytidine
Affected / at Risk (%) # Events
Total   13/16 (81.25%)    
Blood and lymphatic system disorders   
Blood/Bone Marrow - Other (Specify, death-died of progressive MDS)  1 [1]  4/16 (25.00%)  4
Blood/Bone Marrow- Other  1 [2]  4/16 (25.00%)  4
Infection  1 [3]  1/16 (6.25%)  1
Infection  1 [4]  2/16 (12.50%)  2
Opportunistic infection associated with >=Grade 2 Lymphopenia  1 [5]  1/16 (6.25%)  1
Gastrointestinal disorders   
Pain - Abdomen NOS  1 [6]  1/16 (6.25%)  1
Nausea  1 [7]  1/16 (6.25%)  2
Perforation  1 [8]  1/16 (6.25%)  1
Hepatobiliary disorders   
Cholecystitis  1 [9]  1/16 (6.25%)  1
Infections and infestations   
Died of Sepsis  1  3/16 (18.75%)  3
Febrile Neutropenia  1 [10]  1/16 (6.25%)  1
Investigations   
Fatigue  1 [11]  1/16 (6.25%)  1
Nervous system disorders   
Seizure  1 [12]  1/16 (6.25%)  2
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1 [13]  1/16 (6.25%)  1
Hemorrhage  1 [14]  1/16 (6.25%)  1
Skin and subcutaneous tissue disorders   
Myositis  1 [15]  1/16 (6.25%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 4.0
[1]
Death- died of progressive MDS
[2]
progression/relapse of MDS/AML
[3]
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) - Skin (cellulitis) Primary Attribution:Possible Detailed Attribution:Other Drug: 5-Azacytidine
[4]
Infection with unknown ANC
[5]
patient admitted 3/12/12 for fever and mental status changes, confusion worsened and patient found to have basal ganglia hemorrhage secondary to toxoplasmosis, died in paliative care unit 4/17/12
[6]
Primary Attribution: Unrelated Detailed Attribution: Other Drug: 5-Azacytidine antibiotics, supportive care Grade 2
[7]
Primary Attribution: Unrelated Detailed Attribution: Other Drug: 5-Azacytidine
[8]
Perforation, GI - Colon
[9]
Primary Attribution: Unrelated Detailed Attribution: Other Drug: 5-Azacytidine Admitted for abdominal pain, found to have acute cholecystitis and had lap cholycystectomy.
[10]
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection)(ANC <1.0 x 10e9/L, fever >=38.5 degrees C)
[11]
Fatigue (asthenia, lethargy, malaise) Primary Attribution: Unrelated Detailed Attribution: Other Drug: 5-Azacytidine
[12]
Primary Attribution: Unlikely Detailed Attribution: Other Pt with long history of seizure disorder had single seizure. Was seen in ED and discharged to home
[13]
Dyspnea (shortness of breath) Primary Attribution: Possible Detailed Attribution: Investigational Therapy Drug: 5-Azacytidine
[14]
Hemorrhage/Bleeding
[15]
Myositis (inflammation/damage of muscle)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm A: 5-azacytidine
Affected / at Risk (%) # Events
Total   0/16 (0.00%)    
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
Layout table for Results Point of Contact information
Name/Title: John M. McCarty, MD
Organization: Massey Cancer Center
Phone: 804-828-4360
EMail: jmccarty@vcu.edu
Layout table for additonal information
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00721214     History of Changes
Other Study ID Numbers: MCC-11328
First Submitted: July 22, 2008
First Posted: July 24, 2008
Results First Submitted: April 29, 2015
Results First Posted: August 3, 2015
Last Update Posted: March 2, 2016