Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Congenital Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Severe Combined Immunodeficiency; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome
MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Preleukemia; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell, Marginal Zone; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Mycosis Fungoides; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Sezary Syndrome; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Waldenstrom Macroglobulinemia; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myelomonocytic, Juvenile; Polycythemia Vera; Lymphoma, Large-Cell, Anaplastic; Leukemia, Hairy Cell; Leukemia, Myeloid, Chronic-Phase; Lymphomatoid Granulomatosis; Leukemia, Myeloid, Accelerated Phase; Lymphoma, Extranodal NK-T-Cell; Leukemia, Large Granular Lymphocytic; Shwachman-Diamond Syndrome; Hemoglobinuria; Anemia; Myelodysplastic Syndromes; Thrombocytopenia; Primary Myelofibrosis; Neutropenia; Myeloproliferative Disorders; Anemia, Aplastic; Polycythemia; Lymphoproliferative Disorders; Hemoglobinuria, Paroxysmal; Immunoblastic Lymphadenopathy; Myelodysplastic-Myeloproliferative Diseases; Anemia, Diamond-Blackfan; Wiskott-Aldrich Syndrome; Severe Combined Immunodeficiency; Syndrome; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well giving fludarabine phosphate, melphalan, and low-dose
      total-body irradiation (TBI) followed by donor peripheral blood stem cell transplant (PBSCT)
      works in treating patients with hematologic malignancies. Giving chemotherapy drugs such as
      fludarabine phosphate and melphalan, and low-dose TBI before a donor PBSCT helps stop the
      growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting
      the donor's stem cells. When the healthy stem cells from the donor are infused into the
      patient they may help the patient's bone marrow make stem cells, red blood cells, white blood
      cells, and platelets. Sometimes the transplanted cell from a donor can make an immune
      response against the body's normal cells. Giving tacrolimus, mycophenolate mofetil (MMF), and
      methotrexate after transplant may stop this from happening
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the transplant related mortality (TRM) of this reduced-intensity
      transplantation (RIT) combination, fludarabine (fludarabine phosphate), melphalan, and TBI in
      a patient population usually not eligible for a full a myeloablative allogeneic hematopoietic
      stem cell transplantation (HSCT).

      SECONDARY OBJECTIVES:

      I. To evaluate clinical response, progression free survival (PFS) at one year, engraftment
      rate, and graft-versus-host disease (GvHD) incidence with the proposed RIT regimen across a
      variety of hematological conditions.

      II. Correlative studies will include chimerism analysis by molecular analysis and evaluation
      of immune reconstitution by cytomegalovirus (CMV) dextramer analysis using flow cytometry.

      OUTLINE: PREPARATIVE REGIMEN:

      Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2
      and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI twice daily (BID)
      on day -1.

      TRANSPLANTATION:

      Patients undergo allogeneic PBSCT on day 0.

      GvHD PROPHYLAXIS:

      Patients receive tacrolimus IV or orally (PO) BID on days -1 to 100 with taper over 4-6
      months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15-30 minutes
      on days 1, 3, and 6. After completion of study treatment, patients are followed up
      periodically.
    

Intervention name(s): fludarabine phosphate; melphalan; total-body irradiation; tacrolimus; mycophenolate mofetil; methotrexate; laboratory biomarker analysis; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention type(s): Drug; Drug; Radiation; Drug; Drug; Drug; Other; Procedure; Procedure
Intervention description(s): Given IV; Given IV; Undergo TBI; Given IV or PO; Given IV or PO; Given IV; Correlative studies; Undergo allogeneic PBSCT; Undergo PBSCT
Other intervention name(s): 2-F-ara-AMP; Beneflur; Fludara; Alkeran; CB-3025; L-PAM; L-phenylalanine mustard; L-Sarcolysin; TBI; FK 506; Prograf; Cellcept; MMF; amethopterin; Folex; methylaminopterin; Mexate; MTX; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell
Intervention MeSH terms: Mycophenolic Acid; Methotrexate; Fludarabine phosphate; Fludarabine; Melphalan; Tacrolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment