Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer
Condition: Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in
      chemotherapy use different ways to stop cancer cells from dividing so they stop growing or
      die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the
      doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

      PURPOSE: Phase II trial to study the effectiveness of combining total-body irradiation with
      fludarabine and donor peripheral stem cell transplantation in treating patients who have
      hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the response rate and duration of response in patients with low-risk
           hematologic malignancies treated with low-dose total-body irradiation (TBI) and
           fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a
           slow immunosuppression taper and donor leukocyte infusions (DLI).

        -  Determine the response rate and duration of response in patients with high-risk
           hematologic malignancies treated with low-dose TBI and fludarabine followed by
           HLA-matched allogeneic stem cell transplantation followed by a faster immunosuppression
           taper and DLI.

        -  Determine the incidence and extent of graft-versus-host disease, regimen-related
           toxicity, and engraftment in patients treated with these regimens.

        -  Assess the quality of life of patients treated with these regimens.

      OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 groups (high-risk vs
      low-risk hematologic malignancy). The high-risk group includes acute myelogenous leukemia,
      myelodysplastic syndromes, accelerated phase chronic myelogenous leukemia (CML), second
      chronic phase CML, and non-Hodgkin's lymphoma. The low-risk group includes Hodgkin's
      lymphoma, first chronic phase CML, multiple myeloma, and chronic lymphocytic leukemia.

      Patients receive fludarabine IV on days -4 to -2. Patients undergo total-body irradiation on
      day 0 followed by allogeneic stem cell transplantation. Patients also receive oral
      mycophenolate mofetil on days 0-28.

      High-risk patients receive oral cyclosporine twice daily on days -2 to day 60. Patients with
      persistent disease, T-cell chimerism, and no graft-vs-host disease (GVHD) on day 90 receive
      up to 3 doses of donor leukocyte infusion (DLI) over the next 4 months.

      Low-risk patients receive oral cyclosporine twice daily on days -2 to day 150. Patients with
      persistent disease, T-cell chimerism, and no GVHD on day 180 receive up to 3 doses of DLI
      over the next 4 months.

      Quality of life is assessed at baseline and at 1, 3, 6, 9, 12, 18, and 24 months.

      Patients are followed at 1, 3, 6, 9, and 12 months and then annually for 2 years.

      PROJECTED ACCRUAL: A total of 120 patients (60 per group) will be accrued for this study.
    

Intervention name(s): therapeutic allogeneic lymphocytes; cyclosporine; fludarabine phosphate; mycophenolate mofetil; allogeneic bone marrow transplantation; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Cyclosporins
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent adult Hodgkin lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; adult acute myeloid leukemia in remission; recurrent grade 3 follicular lymphoma; recurrent adult diffuse large cell lymphoma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; recurrent mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; refractory multiple myeloma; stage I mantle cell lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; refractory chronic lymphocytic 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)