Reduced Intensity Conditioning Versus Myeloablative Conditioning for Acute Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

Location:

Rochester, MN., Phoenix/Scottsdale, AZ.

Trial status:

Open for Enrollment

Why is this study being done?

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.

Who is eligible to participate?

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 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 ALT and AST less than or equal to 3 times the upper limit of normal.; c)Pulmonary function: DLCO greater than or equal to 40% and 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 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 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.

Last updated:

4/2/2013

NCT ID:

NCT01339910

IRB Number:

11-002298