Radiolabeled Monoclonal Antibody, Cyclophosphamide, and Total Body Irradiation Followed By Donor Stem Cell Transplantation in Treating Patients With Advanced Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and either kill them or
      deliver radioactive cancer-killing substances to them without harming normal cells. Drugs
      used in chemotherapy work in different ways to stop cancer cells from dividing so they stop
      growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Donor stem
      cell transplantation may be able to replace immune cells that were destroyed by radiolabeled
      monoclonal antibody therapy, chemotherapy and radiation therapy.

      PURPOSE: Phase II trial to study the effectiveness of combining radiolabeled monoclonal
      antibody with cyclophosphamide and total-body irradiation followed by donor stem cell
      transplantation in treating patients who have advanced acute myeloid leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the efficacy, in terms of overall survival and disease-free survival, and
           toxicity of cyclophosphamide and total body irradiation in patients with acute myeloid
           leukemia beyond first remission receiving HLA-matched related or unrelated hematopoietic
           stem cell transplantation.

        -  Determine the maximum tolerated dose (MTD) of iodine I 131 monoclonal antibody BC8 (I131
           MOAB BC8) in these patients.

        -  Estimate the MTD of radiation delivered by I 131 MOAB BC8 to marrow of these patients
           and assess the effects on growth of marrow stroma in vitro.

      OUTLINE: This is radiation dose-escalation study. Patients are stratified according to
      available donor (related vs unrelated).

      Patients receive a biodistribution dose of iodine I 131 monoclonal antibody BC8 (I131 MOAB
      BC8) IV, then a therapeutic dose of I131 MOAB BC8 IV 6-14 days later (day -12). Patients
      undergo total body irradiation twice daily on days -6 to -4. Patients receive
      cyclophosphamide IV on days -3 and -2. Bone marrow cells (or peripheral blood stem cells) are
      infused on day 0.

      Patients with CNS leukemic involvement receive intrathecal methotrexate twice before the
      transplantation then every other week for 8 weeks beginning on day 32. These patients also
      receive cranial irradiation beginning on day 32.

      Cohorts of 4 patients each receive escalating doses of iodine I 131 attached to a standard
      dose of monoclonal antibody BC8 until the maximum tolerated dose (MTD) is determined. The MTD
      is defined as the radiation dose preceding that at which 2 of up to 6 patients experience
      graft failure.

      Patients are followed at 6, 9, and 12 months, every 6 months for 1 year, and then annually
      thereafter.

      PROJECTED ACCRUAL: A total of 40 patients (20 per stratum) will be accrued for this study
      within 4 years.
    

Intervention name(s): cyclophosphamide; methotrexate; allogeneic bone marrow transplantation; peripheral blood stem cell transplantation; iodine I 131 monoclonal antibody BC8; radiation therapy
Intervention type(s): Drug; Drug; Procedure; Procedure; Radiation; Radiation
Intervention MeSH terms: Cyclophosphamide; Methotrexate; Antibodies; Antibodies, Monoclonal
Primary purpose: Treatment
Keywords: recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; secondary acute myeloid leukemia; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12)