T-Cell-Depleted Allogeneic Stem Cell Transplantation After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Hematologic Malignancies
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Hematologic Neoplasms; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Donor peripheral stem cell transplantation may be able to replace bone marrow and
      immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a
      donor are rejected by the body's normal cells. Eliminating the T cells from the donor cells
      before transplanting them and giving cyclosporine may prevent this from happening.

      PURPOSE: This phase I trial is studying the side effects of T-cell-depleted allogeneic stem
      cell transplantation after immunoablative induction chemotherapy and reduced-intensity
      transplantation conditioning (chemotherapy) in treating patients with hematologic
      malignancies.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine engraftment in patients with hematologic malignancies treated with
           T-cell-depleted allogeneic stem cell transplantation after immunoablative induction
           chemotherapy and reduced-intensity transplantation conditioning.

      Secondary

        -  Determine the incidence of acute graft-versus-host disease (GVHD), and nonrelapse
           mortality (within 100 days after transplantation) in these patients.

        -  Correlate levels of host immunosuppression before transplantation conditioning, as
           evaluated by peripheral blood CD4 counts, with graft rejection/failure within 100 days
           after transplantation and the level of donor hematopoietic chimerism 28 days after
           transplantation in these patients.

        -  Correlate donor-versus-recipient natural killer cell alloreactivity with graft
           rejection/failure, acute GVHD, and relapse of malignant disease in patients treated with
           this regimen.

        -  Determine the development of allospecific cytotoxic T-lymphocytes after transplantation
           in patients with myeloid or lymphoid leukemia.

        -  Correlate serum interleukin-7 and interleukin-15 levels with in vivo changes in host
           lymphocyte subpopulations in these patients during sequential immunoablative
           chemotherapy, before allogeneic stem cell transplantation, and during immune
           reconstitution after transplantation.

      OUTLINE: This is a pilot study.

        -  Induction chemotherapy: Patients receive 1 of 2 induction chemotherapy regimens
           according to diagnosis. Patients with partial response or better after prior therapy
           (i.e., already adequately immune depleted) proceed directly to the transplantation
           preparative regimen.

             -  Regimen A (Hodgkin's lymphoma, non-Hodgkin's lymphoma [except lymphoblastic
                lymphoma], chronic lymphocytic leukemia, prolymphocytic leukemia, or multiple
                myeloma): Patients receive rituximab IV (if they have CD20+ B-cell malignancies) on
                day 1; fludarabine IV over 30 minutes on days 1-4; etoposide, doxorubicin, and
                vincristine IV continuously on days 1-4; cyclophosphamide IV over 30 minutes on day
                5; oral prednisone on days 1-5; and filgrastim (G-CSF) subcutaneously (SC)
                beginning on day 6 and continuing until blood counts recover.

             -  Regimen B (lymphoblastic lymphoma, acute myeloid leukemia, acute lymphoblastic
                leukemia, refractory anemia with excess blasts, myeloproliferative disorders,
                chronic myelomonocytic leukemia, or chronic myelogenous leukemia): Patients receive
                G-CSF SC beginning 24 hours before initiating induction chemotherapy and continuing
                until blood counts recover. Patients also receive fludarabine IV over 30 minutes
                and cytarabine IV over 4 hours on days 1-5.

      For both regimens, treatment repeats every 21 days for 1-2 courses. Patients who achieve
      remission or who have responsive or stable disease after induction chemotherapy then proceed
      to transplantation preparative regimen chemotherapy.

        -  Transplantation preparative regimen chemotherapy: Patients receive fludarabine IV over
           30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3.

        -  Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2
           hours twice daily beginning on day -1 and continuing IV or orally until day 100.
           Patients with no acute GVHD at day 100 taper cyclosporine over 12 weeks.

        -  Allogeneic stem cell transplantation (SCT): Patients undergo T-cell-depleted allogeneic
           peripheral blood SCT on day 0. Patients receive G-CSF SC beginning on day 0 and
           continuing until blood counts recover.

        -  Donor lymphocyte infusion (DLI): Patients with persistent or progressive malignant
           disease after transplantation or mixed chimerism that does not improve after tapering or
           discontinuing immunosuppression therapy may receive DLI. DLI may be administered alone
           or in combination with chemotherapy. DLI repeats every 4 weeks until adequate donor
           chimerism is achieved or until GVHD develops.

      Patients are followed at 28 and 100 days and then at 6, 9, 12, 18, and 24 months.

      PROJECTED ACCRUAL: A total of 6-20 patients will be accrued for this study within 2 years.
    

Intervention name(s): filgrastim; graft-versus-tumor induction therapy; rituximab; therapeutic allogeneic lymphocytes; cyclophosphamide; cyclosporine; cytarabine; doxorubicin hydrochloride; etoposide; fludarabine phosphate; prednisone; vincristine sulfate; peripheral blood stem cell transplantation
Intervention type(s): Biological; Biological; Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Cytarabine; Cyclosporine; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Fludarabine; Fludarabine phosphate; Etoposide; Vincristine; Cyclosporins
Primary purpose: Treatment
Keywords: prolymphocytic leukemia; accelerated phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; de novo myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; secondary acute myeloid leukemia; recurrent adult Hodgkin lymphoma; refractory anemia with excess blasts; refractory multiple myeloma; primary myelofibrosis; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult Burkitt lymphoma; recurrent mantle cell lymphoma; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; chronic myelomonocytic leukemia; polycythemia vera; essential thrombocythemia; stage II multiple myeloma; stage III multiple myeloma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; 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)