Targeted Marrow Irradiation, Fludarabine Phosphate, and Busulfan Before Donor Progenitor Cell Transplant in Treating Patients With Hematologic Malignancies
Condition: Acute Myeloid Leukemia; Hematologic Malignancies; Acute Lymphocytic Leukemia; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia; Chronic Myeloid Leukemia; Myelofibrosis; Myeloproliferative Syndrome
MeSH terms: Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and best dose of targeted marrow irradiation when
      given with fludarabine phosphate and busulfan before donor progenitor cell transplant in
      treating patients with hematologic malignancies. Targeted marrow irradiation is a type of
      specialized radiation therapy that delivers a high dose of radiation directly to the cancer
      cells, which may kill more cancer cells and cause less damage to normal cells. Giving
      targeted marrow irradiation and chemotherapy drugs, such as fludarabine phosphate and
      busulfan, before a donor progenitor cell transplant may help stop the growth of cancer cells.
      It may also stop the patient's immune system from rejecting the donor's progenitor cells.
      When the healthy progenitor cells from a donor are infused into the patient they may help the
      patient's bone marrow make progenitor cells, red blood cells, white blood cells, and
      platelets.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose of targeted marrow irradiation given in
      combination with fludarabine (fludarabine phosphate) and busulfan as conditioning regimen for
      allogeneic hematopoietic progenitor cell transplantation.

      SECONDARY OBJECTIVES:

      I. To describe the toxicity profile of the conditioning regimen of targeted marrow
      irradiation (TMI), fludarabine and busulfan for allogeneic hematopoietic progenitor
      transplantation.

      II. To describe the use of two techniques of delivering TMI, volumetric modulated arc therapy
      (VMAT) and TomoTherapy, on patient's computed tomography (CT) simulation images and describe
      differences in organ avoidance and target coverage, planning time, and treatment delivery
      time.

      III. To determine the disease response status 100 days after allogeneic hematopoietic
      progenitor cell transplantation with the conditioning regimen of TMI, fludarabine and
      busulfan.

      IV. To determine the rates of acute graft versus host disease after allogeneic hematopoietic
      progenitor cell transplantation with the conditioning regimen of TMI, fludarabine and
      busulfan.

      OUTLINE: This is a dose-escalation study of TMI.

      CONDITIONING: Patients undergo TMI twice daily (BID) on days -10 to -7. Patients also receive
      fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and busulfan IV or
      orally (PO) on days -5 and -4.

      TRANSPLANT: Patients undergo allogeneic hematopoietic progenitor cell transplant on day 0.

      GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on
      days -3 and -2, tacrolimus IV or PO beginning on day -1 for at least 6 months with taper
      beginning at 4 months, and methotrexate IV on days 1, 3, 6, and 11.

      After completion of study treatment, patients are followed up at 100 days, 6 months, and 12
      months.
    

Intervention name(s): total marrow irradiation; fludarabine phosphate; busulfan; myeloid progenitor cell transplantation; anti-thymocyte globulin; tacrolimus; methotrexate; laboratory biomarker analysis
Intervention type(s): Radiation; Drug; Drug; Procedure; Biological; Drug; Drug; Other
Intervention description(s): Undergo TMI; Given IV; Given IV or PO; Undergo allogeneic hematopoietic progenitor cell transplant; Given IV; Given IV or PO; Given IV; Correlative studies
Other intervention name(s): 2-F-ara-AMP; Beneflur; Fludara; BSF; BU; Misulfan; Mitosan; Myeloleukon; MPCT; ATG; ATGAM; lymphocyte immune globulin; Thymoglobulin; FK 506; Prograf; amethopterin; Folex; methylaminopterin; Mexate; MTX
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Fludarabine; Busulfan; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Immunoglobulins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment