Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)
Condition: Leukemia, Myelocytic, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Preleukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: Fludarabine and Busulfan; Fludarabine and Melphalan; Busulfan and Fludarabine; Busulfan and Cyclophosphamide; Cyclophosphamide and Total Body Irradiation
Intervention description: (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; (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; (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); (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); (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)
Intervention MeSH terms: Vidarabine; Cyclophosphamide; Melphalan; Busulfan; Fludarabine; Fludarabine phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 272.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Acute Myelogenous Leukemia; Myelodysplastic Syndrome

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age equal or less than 65 years old and equal to or greater than 18 years old.

          -  Patients with the diagnosis of MDS or AML with fewer than 5% myeloblasts in the bone
             marrow and no leukemic myeloblasts in the peripheral blood on morphologic analysis
             performed within 30 days of start of the conditioning regimen enrollment.

          -  For patients receiving treatment of their MDS or AML prior to transplantation:
             a)Interval between the start of the most recent cycle of conventional cytotoxic
             chemotherapy and enrollment must be at least 30 days; b)Interval between completing
             treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and
             enrollment must be at least 10 days.

          -  Patients must have a related or unrelated bone marrow or peripheral blood donor who is
             human leukocyte antigen (HLA)-matched at 7 or 8 of 8 HLA-A, -B, -C and -DRB1 at high
             resolution using DNA-based typing.

          -  HCT-Specific Comorbidity Index Score (HCT-CI) less than or equal to 4.

          -  Organ function: a) Cardiac function: Ejection fraction greater than or equal to 40%;
             b) Hepatic function: total bilirubin less than or equal to 2 times the upper limit of
             normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less
             than or equal to 3 times the upper limit of normal.; c)Pulmonary function: Diffusing
             capacity of the lung for carbon monoxide (DLCO) greater than or equal to 40% and
             forced expiratory volume in one second (FEV1) greater than or equal to 50% (corrected
             for hemoglobin).

          -  Creatinine clearance greater than or equal to 50mL/min based on the Cockcroft-Gault
             formula.

          -  Signed informed consent.

        Exclusion Criteria:

          -  Prior allograft or prior autograft.

          -  Symptomatic coronary artery disease.

          -  Leukemia involvement in the central nervous system (CNS) within 4 weeks of enrollment
             for patients with a history of prior CNS leukemia involvement (i.e., leukemic blasts
             previously detected in the cerebral spinal fluid).

          -  Karnofsky Performance Score less than 70.

          -  Patients receiving supplemental oxygen.

          -  Planned use of donor lymphocyte infusion (DLI) therapy.

          -  Patients with uncontrolled bacterial, viral or fungal infections (undergoing
             appropriate treatment and with progression of clinical symptoms).

          -  Patients seropositive for the human immunodeficiency virus (HIV).

          -  Patients with prior malignancies, except resected basal cell carcinoma or treated
             cervical carcinoma in situ. Cancer treated with curative intent greater than 5 years
             previously. Cancer treated with curative intent less than 5 years previously will not
             be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.

          -  Females who are pregnant or breastfeeding.

          -  Fertile men and women unwilling to use contraceptive techniques during and for 12
             months following treatment.