Cyclophosphamide and/or Mycophenolate Mofetil With or Without Tacrolimus in Treating Patients Who Are Undergoing a Donor Bone Marrow or Peripheral Stem Cell Transplant for Hematologic Cancer
Condition: Chronic Myeloproliferative Disorders; Graft Versus Host Disease; 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; Graft vs Host Disease; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy
      before a donor bone marrow or 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). Sometimes the transplanted cells from a donor can also
      make an immune response against the body's normal cells. Giving cyclophosphamide,
      mycophenolate mofetil, and tacrolimus after transplant may stop this from happening.

      PURPOSE: This phase I trial is studying cyclophosphamide and/or mycophenolate mofetil with or
      without tacrolimus to see which is the best regimen in treating patients who are undergoing a
      donor bone marrow or stem cell transplant for hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Determine a minimal (short-duration) post-transplant immunosuppression regimen
           comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus that
           results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease (GVHD)
           in patients with hematologic malignancies undergoing nonmyeloablative allogeneic bone
           marrow or peripheral blood stem cell transplantation from an HLA-identical related
           donor.

        -  Determine the post-transplant immunosuppression regimen that results in < 10% incidence
           of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in
           these patients.

        -  Determine the incidence and severity of acute GVHD in patients treated with these
           regimens.

        -  Determine the frequency of mixed chimerism in patients treated with these regimens.

      OUTLINE:

        -  Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem
           cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and
           undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or
           PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF)
           beginning on day 5 and continuing until at least day 15 or until blood counts recover.

        -  Sequentially increasing levels of post-transplant immunosuppression: Cohorts of patients
           are enrolled into 1 of the following regimens:

             -  Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on day
                3 only.

             -  Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil
                (MMF) once on day 3 and then twice daily on days 4-32.

             -  Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on
                days 3 and 4 and MMF twice daily on days 4-33.

             -  Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF
                as in regimen 3.

             -  Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF
                as in regimen 3 and tacrolimus twice daily on days 4-33.

      Cohorts of approximately 10-20 patients receive sequentially increasing levels of
      post-transplant immunosuppression until a minimal (short-duration) post-transplant
      immunosuppression regimen is identified. The minimal post-transplant immunosuppression
      regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II
      or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to engraft
      60 days post-transplantation. Once the minimal post-transplant immunosuppression regimen is
      identified, an additional 10 patients are treated with that regimen.

      Patients are followed for 60 days after transplantation.

      PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
    

Intervention name(s): filgrastim; cyclophosphamide; fludarabine phosphate; mycophenolate mofetil; tacrolimus; allogeneic bone marrow transplantation; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tacrolimus
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: graft versus host disease; 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); adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; chronic idiopathic myelofibrosis; chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; previously treated myelodysplastic syndromes; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; stage II multiple myeloma; stage III adult Hodgkin lymphoma; stage III chronic lymphocytic leukemia; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III multiple myeloma; stage III small lymphocytic lymphoma; stage IV adult Hodgkin lymphoma; stage IV chronic lymphocytic leukemia; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV small lymphocytic lymphoma; stage II mycosis fungoides/Sezary syndrome; stage III mycosis fungoides/Sezary syndrome; stage IV mycosis fungoides/Sezary syndrome; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; refractory cytopenia with multilineage dysplasia; primary systemic amyloidosis; de novo myelodysplastic syndromes; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia