Monoclonal Antibody Therapy, Cyclophosphamide, and Total-Body Irradiation Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Recurrent Acute Lymphocytic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver
      cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy
      use 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. Peripheral stem cell transplantation
      may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy
      used to kill cancer cells.

      PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy,
      cyclophosphamide, and total-body irradiation followed by peripheral stem cell transplantation
      in treating patients who have advanced recurrent acute lymphocytic leukemia.
    

Detailed description: 
      OBJECTIVES: I. Assess the efficacy and toxicity of iodine I 131 monoclonal antibody BC8,
      cyclophosphamide, and total body irradiation in patients with advanced acute lymphocytic
      leukemia who are receiving HLA matched related or unrelated bone marrow transplantation. II.
      Determine the maximum tolerated dose (MTD) of iodine I 131 monoclonal antibody BC8 in these
      patients. III. Estimate the MTD of radiation delivered by iodine I 131 monoclonal antibody
      BC8 to the marrow. IV. Study the influence of marrow cellularity, level of antigen expression
      by leukemic cells, and degree of antigen saturation by antibody on the biodistribution of
      iodine I 131 monoclonal antibody BC8 in these patients.

      OUTLINE: This is a dose-escalation study. All patients receive a test dose of iodine I 131
      monoclonal antibody BC8 (MOAB BC8) IV over several hours 6-14 days prior to the therapeutic
      dose. Patients receive the therapeutic dose of iodine I 131 MOAB BC8 IV over several hours on
      day -11, total body irradiation over 30-40 minutes twice a day on days -6 to -4, and
      cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo allogenic bone marrow
      transplantation on day 0. Patients receive intrathecal methotrexate twice prior to
      transplantation and then every other week for 4 weeks beginning on day 32 posttransplant.
      Cohorts of 4 patients receive escalating doses of iodine I 131 monoclonal antibody until the
      maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
      which 2 of 4 patients experience dose-limiting toxicity. Patients are followed for the first
      100 days, at 6, 9 and 12 months, every 6 months for 1 year, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.
    

Intervention name(s): cyclophosphamide; methotrexate; allogeneic bone marrow transplantation; iodine I 131 monoclonal antibody BC8; radiation therapy
Intervention type(s): Drug; Drug; Procedure; Radiation; Radiation
Intervention MeSH terms: Cyclophosphamide; Methotrexate; Antibodies; Antibodies, Monoclonal
Primary purpose: Treatment
Keywords: recurrent childhood acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia; adult acute lymphoblastic leukemia in remission; childhood acute lymphoblastic leukemia in remission