Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome
Study type: Interventional

Summary: 
      RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor
      bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells.
      It also stops the patient's immune system from rejecting the donor's stem cells. The donated
      stem cells may replace the patient's immune system and help destroy any remaining cancer
      cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor
      lymphocyte infusion) after the transplant may help increase this effect. Sometimes the
      transplanted cells from a donor can also make an immune response against the body's normal
      cells. Giving antithymocyte globulin before transplant and methotrexate and tacrolimus after
      the transplant may stop this from happening.

      PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in
      treating older or frail patients with hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety of non-myeloablative allogeneic peripheral blood stem cell
           transplantation, in terms of regimen-related organ toxicity and toxicity from acute
           graft-vs-host disease (GVHD), in older or medically frail patients with high-risk
           indolent hematologic malignancies.

        -  Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years
           post-transplantation in these patients.

      Secondary

        -  Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year
           post-transplantation in these patients.

        -  Determine the incidence and severity of chronic GVHD in older and medically infirm
           patients treated with this regimen.

        -  Determine the safety and efficacy of collecting peripheral blood stem cells from older
           donors (age > 60 years).

        -  Determine the need and efficacy of donor lymphocyte infusions in patients with residual
           disease after transplant.

      OUTLINE:

        -  Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on
           days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and
           anti-thymocyte globulin IV over 8 hours on days -4 to -1.

        -  Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation
           on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and
           continuing until blood counts recover.

        -  Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12
           hours or IV continuously beginning on day -2 and continuing until day 90, followed by a
           taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1,
           3, 6, and 11.

        -  Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months
           post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of
           GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of
           persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD
           after the first DLI.

      After completion of study therapy, patients are followed periodically for 5 years.

      PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
    

Intervention name(s): anti-thymocyte globulin; filgrastim; therapeutic allogeneic lymphocytes; busulfan; fludarabine phosphate; methotrexate; tacrolimus; nonmyeloablative allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention type(s): Biological; Biological; Biological; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Fludarabine; Busulfan; Tacrolimus; Antilymphocyte Serum
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage III adult diffuse small cleaved cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; noncontiguous stage II marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; noncontiguous stage II mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; stage II multiple myeloma; stage III multiple myeloma; chronic phase chronic myelogenous leukemia; primary myelofibrosis; polycythemia vera; prolymphocytic leukemia; stage II adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; chronic myelomonocytic leukemia; adult acute myeloid leukemia in remission; secondary acute myeloid leukemia; Waldenström macroglobulinemia; essential thrombocythemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; 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); noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; stage I multiple myeloma