Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)
|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
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Myelocytic, Acute||Drug: Fludarabine and Busulfan Drug: Fludarabine and Melphalan Drug: Busulfan and Fludarabine Drug: Busulfan and Cyclophosphamide Drug: Cyclophosphamide and Total Body Irradiation||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||272 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, Multi-Center, Phase III Study of Allogeneic Stem Cell Transplantation Comparing Regimen Intensity in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia (BMT CTN #0901)|
|Actual Study Start Date :||June 2011|
|Actual Primary Completion Date :||January 16, 2017|
|Actual Study Completion Date :||October 16, 2017|
Experimental: Reduced Intensity Conditioning (RIC)
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Drug: Fludarabine and Busulfan
Other Name: Fludara and Busulfex
Drug: Fludarabine and Melphalan
Other Name: Fludara and Alkeran
Active Comparator: Myeloablative Conditioning Regimen (MAC)
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Drug: Busulfan and Fludarabine
Other Name: Busulfex and Fludara
Drug: Busulfan and Cyclophosphamide
Other Name: Busulfex and Cytoxan
Drug: Cyclophosphamide and Total Body Irradiation
Other Name: Cytoxan and radiation
- Percentage of Participants With Overall Survival (OS) [ Time Frame: 18 months post-randomization ]Overall survival is defined as survival of death from any cause.
- Percentage of Participants With Relapse-Free Survival (RFS) [ Time Frame: 18 months post-randomization ]Relapse-free survival is defined as survival without relapse of the primary disease.
- Percentage of Participants With Disease Relapse [ Time Frame: 18 months post-randomization ]Disease Relapse is defined as relapse of the primary disease.
- Percentage of Participants With Treatment-related Mortality [ Time Frame: 18 months post-randomization ]Treatment-related mortality is defined as death without a previous relapse of the primary disease.
- Percentage of Participants With Neutrophil and Platelet Engraftment [ Time Frame: Days 28 and 60 post-transplant ]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.
- Number of Participants With Donor Cell Engraftment [ Time Frame: Days 28 and 100 and 18 months post-transplant ]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.
- Percentage of Participants With Acute Graft Versus Host Disease (GVHD) [ Time Frame: Day 100 post-transplant ]
Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:
0: No rash
- Rash <25% of body surface area
- Rash on 25-50% of body surface area
- Rash on > 50% of body surface area
- Generalized erythroderma with bullous formation
Liver stage (based on bilirubin level)*:
0: <2 mg/dL
- 2-3 mg/dL
- 3.01-6 mg/dL
- 6.01-15.0 mg/dL
- >15 mg/dL
0: No diarrhea or diarrhea <500 mL/day
- Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
- Diarrhea 1000-1499 mL/day
- Diarrhea >1500 mL/day
- Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.
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
- Percentage of Participants With Chronic GVHD [ Time Frame: 18 months post-transplant ]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.
- Number of Participants With Chronic GVHD Severity [ Time Frame: 18 months post-transplant ]Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.
- Number of Participants With Primary Graft Failure [ Time Frame: 28 days post-transplant ]Primary graft failure is defined by lack of neutrophil engraftment.
- Number of Participants With Secondary Graft Failure [ Time Frame: 18 months post-transplant ]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.
- Number of Participants With Maximum Grade 3-5 Toxicities [ Time Frame: 18 months ]
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
- Infection Type [ Time Frame: 18 months post-transplant ]The number and types of infection events reported are tabulated.
- Number of Participants With Infections [ Time Frame: 18 months post-transplant ]
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.
- Number of Participants With Cause of Death [ Time Frame: 18 months post-randomization ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01339910
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|Study Director:||Mary Horowitz, MD||Center for International Blood and Marrow Transplant Research|