S9920 Busulfan Compared With Cyclophosphamide in Patients Undergoing Total-Body Irradiation Plus Peripheral Stem Cell Transplantation for Advanced Myelodysplastic Syndrome or Related Acute Myeloid Leukemia
Condition: Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were
      destroyed by chemotherapy or radiation therapy used to kill tumor cells. It is not yet known
      if total-body irradiation plus peripheral stem cell transplantation is more effective with
      busulfan or with cyclophosphamide for myelodysplastic syndrome or acute myeloid leukemia.

      PURPOSE: Randomized phase III trial to compare the effectiveness of busulfan with that of
      cyclophosphamide in patients undergoing total-body irradiation plus peripheral stem cell
      transplantation for advanced myelodysplastic syndrome or related acute myeloid leukemia.
    

Detailed description: 
      OBJECTIVES: I. Compare event free survival after total body irradiation (TBI) plus busulfan
      versus TBI plus cyclophosphamide followed by allogeneic peripheral blood stem cell
      transplantation in patients with advanced myelodysplastic syndrome (MDS) or MDS related acute
      myeloid leukemia. II. Determine the distribution of pharmacokinetic parameters for busulfan
      in those patients randomized to the busulfan treatment arm. III. Investigate the prognostic
      significance for event free survival of prior history of red cell transfusions, cytogenetic
      pattern, and of functional drug resistance at diagnosis in these patients. IV. Estimate the
      frequencies of cytogenetic and genetic changes during disease progression in these patients.

      OUTLINE: This a randomized, multicenter study. Patients are stratified according to age (40
      and under vs 41-55) and diagnosis and International Prognostic Scoring System (IPSS) risk
      group (myelodysplastic syndrome (MDS)/IPSS - intermediate 1 vs MDS/IPSS - intermediate 2 vs
      MDS/IPSS high risk vs MDS related acute myeloid leukemia). Patients are randomized to one of
      two treatment arms. Arm I: Patients receive busulfan IV over 2 hours every 6 hours on days -7
      to -4 for a total of 16 doses. Arm II: Patients receive cyclophosphamide IV over 2 hours on
      days -5 and -4. Patients receive total body irradiation (TBI) twice a day on days -3 to -1;
      peripheral blood stem cell transplantation from genotypically HLA identical sibling on day 0;
      cyclosporine IV every 12 hours on days -1 to 60, and then tapering in the absence of graft
      versus host disease; and methotrexate IV on days 1, 3, 6, and 11. Patients are followed every
      6 months for 5 years.

      PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this
      study over 5 years.
    

Intervention name(s): busulfan; cyclophosphamide; cyclosporine; methotrexate; allogeneic bone marrow transplantation; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention description(s): arm 1: 0.44 mg/kg every 6 hours, IV over 2 hours, day -7 to -4; arm 2: 60 mg/kg every 24 hrs for 2 doses, IV over 2 hrs, days -5 and -4; both arms per published schedule; GVHD: 15 mg/m2 day 1, 10 mg/m2 day 3, 6 and 11 by IV; day 0; both arms: 1200 cGy total dose (6 x 200 fractions)
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Busulfan; Methotrexate; Cyclosporins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: untreated adult acute myeloid leukemia; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood myelodysplastic syndromes