Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer
Condition: Leukemia; Lymphoma; Myelodysplastic Syndromes
MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, before a
      donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps
      stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem
      cells from a donor are infused into the patient they may help the patient's bone marrow make
      stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted
      cells from a donor can make an immune response against the body's normal cells. Giving
      high-dose cyclophosphamide together with tacrolimus and mycophenolate mofetil after
      transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well combination chemotherapy works when given
      together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil,
      and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To estimate the incidence of graft rejection and severe graft-versus-host disease after
           myeloablative HLA-mismatched peripheral blood stem cell transplantation (PBSCT) from
           first-degree relatives in patients with high-risk hematologic malignancies.

      Secondary

        -  To estimate overall survival, relapse, non-relapse mortality, and event-free survival in
           these patients.

        -  To characterize additional hematologic and non-hematologic toxicities of myeloablative
           haploidentical PBSCT.

        -  To characterize donor hematopoietic chimerism in peripheral blood stem cells after
           PBSCT.

      OUTLINE:

        -  Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days
           -7 to -2, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV over 1-2
           hours on days -3 and -2.

        -  Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo infusion
           of unmanipulated peripheral blood stem cells on day 0.

        -  Post-transplant regimen: Patients receive high-dose cyclophosphamide IV over 1-2 hours
           on days 3 and 4, tacrolimus IV over 24 hours or orally twice daily on days 5-180, and
           oral mycophenolate mofetil 3 times daily on days 5-34 followed by a taper to day 90.
           Treatment continues in the absence of disease progression or clinically significant
           graft-vs-host disease.

      After completion of PBSCT, patients are followed periodically for 1 year.
    

Intervention name(s): busulfan; cyclophosphamide; fludarabine phosphate; mycophenolate mofetil; tacrolimus; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention description(s): 110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4); 14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2).; 30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3); 15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD.; 0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD.; Patients to received unmanipulated PBSCs on Day 0; patients to receive unmanipulated PBSCs on day 0
Other intervention name(s): CellCept; Prograf, FK-506; Allo HSCT; allogeneic hematopoietic stem cell transplant
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Tacrolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult Hodgkin lymphoma; stage III adult lymphoblastic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; 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); chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; recurrent adult acute myeloid leukemia; refractory chronic lymphocytic leukemia; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; prolymphocytic leukemia