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
Last Update Posted : December 2, 2017
|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 :||May 2011|
|Primary Completion Date :||January 16, 2017|
|Study Completion Date :||October 16, 2017|
Active Comparator: 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 BusulfexDrug: Fludarabine and Melphalan
Other Name: Fludara and Alkeran
Experimental: 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 FludaraDrug: Busulfan and Cyclophosphamide
Other Name: Busulfex and CytoxanDrug: Cyclophosphamide and Total Body Irradiation
Other Name: Cytoxan and radiation
- Overall Survival [ Time Frame: 18 months ]The primary objective of the trial is to compare 18 month overall survival rates of the two groups of patients starting from the time of randomization to the RIC or MAC arms.
- Disease-Free Survival [ Time Frame: time from randomization to relapse, death, initiation of non-protocol AML or MDS therapy, loss to follow up or end of study whichever comes first ]Disease-free survival will be at different time points. Patients are considered a failure if they die or suffer from disease relapse.
- Treatment-related Mortality [ Time Frame: 18 months ]Treatment-related mortality (TRM) is defined as death occurring in a patient from causes other than disease relapse. Individuals who relapse are censored for the event of TRM.
- Neutrophil and Platelet Engraftment [ Time Frame: 100 days ]Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500 µL 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 and 50,000/µL 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.
- Donor Cell Engraftment [ Time Frame: Day 100 and 18 months post transplantation ]Donor cell engraftment will be assessed by donor recipient chimerism studies. For this protocol, mixed chimerism will be defined as the presence of donor cells, as a proportion of the total population of less than 95% in the peripheral blood or bone marrow. Full donor chimerism is defined as greater than 95% donor donor cells. Mixed or full donor chimerism will be evidence of donor engraftment. For this protocol, graft rejection is defined as the inability to detect or loss of detection of greater than 5% donor cells as a proportion of the total population.
- Acute Graft Versus Host Disease (GVHD) of Grades II-IV and III-IV [ Time Frame: 100 days ]The first day of acute GVHD onset at a certain grade will be used to calculate cumulative incidence curves for that GVHD grade (e.g., if the onset of grade I acute GVHD is on Day 19 post-transplant and onset of grade III is on Day 70 post-transplant, time to grade III is Day 70). This endpoint will be evaluated through 100 days and compared between treatment arms.
- Chronic GVHD [ Time Frame: 18 months ]The first day of chronic GVHD onset will be used to calculate cumulative incidence curves. Rates and severity of chronic GVHD will be compared between treatment arms.
- Incidence of Primary Graft Failure [ Time Frame: 28 days ]This is defined by lack of neutrophil engraftment by 28 days. Rates of primary graft failure will be compared between treatment arms.
- Incidence of Secondary Graft Failure [ Time Frame: 18 months ]This is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts less than 500/µL unresponsive to growth factor therapy. Rates of secondary graft failure will be compared between treatment arms.
- Incidence of Toxicities Greater Than Grade 3 [ Time Frame: 18 months ]All toxicities greater than or equal to Grade 3 will be tabulated by grade for each treatment arm, by type of toxicity as well as the peak grade overall. Toxicity frequencies will be described for each time interval as well as cumulative over time.
- Incidence of Infections [ Time Frame: 6, 12, and 18 months post transplant or until death ]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.
- Immune Reconstitution [ Time Frame: Baseline, 100 days, 12 months and 18 months post transplant ]Quantitative assessments of peripheral blood CD3, CD4, CD8, CD19 and CD56 positive lymphocytes will be done through flow cytometric analysis at baseline , 100 days, 12 months and 18 months post transplantation. Results will be tabulated according to time from transplant.
- Health-related Quality of Life (HQL) [ Time Frame: Prior to transplant, 100 days, 12 and 18 months or until death ]HQL will be described and compared between the two treatment arms over time. The self report questionnaires will be completed prior to transplantation and subsequently at 100 days, 12, and 18 months from randomization or until death. HQL include: FACT-BMT, SF-36, MDASI and EQ-5D.
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|