NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Fanconi Anemia; Aplastic Anemia
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Anemia; Myelodysplastic Syndromes; Anemia, Aplastic; Myeloproliferative Disorders; Fanconi Anemia; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving low doses of chemotherapy before a donor 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 immunosuppressive therapy before or after
      the transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral
      stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood
           stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.

        -  Determine clinical response and overall outcome of patients treated with this regimen.

        -  Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism
           in patients treated with this regimen.

      OUTLINE:

        -  Preparative regimen:

             -  Matched related and unrelated donor transplantation:

                  -  Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and
                     fludarabine IV over 30 minutes on days -5 to -1.

             -  Cord blood transplantation:

                  -  Patients receive the same regimen as above plus anti-thymocyte globulin IV
                     over 4 hours on days -3 to -1.

        -  Graft-vs-host disease (GVHD) prophylaxis:

             -  Matched related and unrelated donor transplantation:

                  -  Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate
                     mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of
                     this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.

             -  Cord blood transplantation:

                  -  Patients receive tacrolimus and MMF in the same regimen as above plus
                     methylprednisolone twice daily on days 1-19 or until blood counts recover.

        -  Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral
           blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF)
           subcutaneously daily beginning on day 7 and continuing until blood counts recover.

        -  Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism
           by day 120 and showing signs of progresson of disease after tacrolimus and MMF
           withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do
           not receive DLI.

      Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for
      5 years.

      PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.
    

Intervention name(s): anti-thymocyte globulin; graft-versus-tumor induction therapy; sargramostim; therapeutic allogeneic lymphocytes; cyclophosphamide; fludarabine phosphate; methylprednisolone; mycophenolate mofetil; tacrolimus; allogeneic bone marrow transplantation; peripheral blood stem cell transplantation; umbilical cord blood transplantation
Intervention type(s): Biological; Biological; Biological; Biological; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Procedure
Intervention description(s): iv; iv; iv; iv; injection; iv; oral; oral; oral; iv; iv; iv
Other intervention name(s): FLUDARA
Intervention MeSH terms: Mycophenolic Acid; Methylprednisolone; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tacrolimus; Antilymphocyte Serum; Sargramostim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: accelerated phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; primary myelofibrosis; de novo myelodysplastic syndromes; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; refractory anemia with excess blasts; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; Waldenstrom macroglobulinemia; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; recurrent adult Hodgkin lymphoma; adult acute myeloid leukemia in remission; secondary acute myeloid leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; childhood acute lymphoblastic leukemia in remission; adult acute lymphoblastic leukemia in remission; noncontiguous stage II adult lymphoblastic lymphoma; refractory multiple myeloma; refractory anemia; refractory chronic lymphocytic leukemia; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; grade 1 follicular lymphoma; grade 2 follicular lymphoma; recurrent/refractory childhood Hodgkin lymphoma; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; 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); childhood myelodysplastic syndromes