Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)
The study is designed as a Phase III, multicenter trial comparing outcomes after allogeneic hematopoietic stem cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) between patients receiving myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) regimens.
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
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|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)|
- Overall Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||November 2017|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
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
Patients randomized to RIC will receive one of two regimen types: the combination of fludarabine (120-180 mg/m^2) and busulfan (less than or equal to 8 mg/kg or IV equivalent) (Flu/Bu) or fludarabine (120-180 mg/m^2) and melphalan (less than 150 mg/m^2) (Flu/Mel). Patient randomized to MAC will receive one of three regimens: busulfan (16 mg/kg oral or 12.8 mg/kg IV equivalent) and cyclophosphamide (120 mg/kg) (Bu/Cy); or, busulfan (16 mg/kg PO or 12.8 mg/kg IV) and fludarabine (120-180 mg/m^2) (Bu/Flu); or, cyclophosphamide (120 mg/kg) and total body irradiation (greater than 1200-1420cGy) (CyTBI). A total of 356 patients (178 to each arm) will be accrued on this study over a period of four years. Patients will be followed for up to 18 months from transplantation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01339910
Show 29 Study Locations
|Study Director:||Mary Horowitz, MD||Center for International Blood and Marrow Transplant Research|