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
Intervention: busulfan; cyclophosphamide; fludarabine phosphate; mycophenolate mofetil; tacrolimus; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention description: 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
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of one of the following high-risk hematologic malignancies:

               -  Chronic myelogenous leukemia meeting one of the following criteria:

                    -  Disease in chronic phase and resistant to available tyrosine kinase
                       inhibitors

                    -  Disease in accelerated phase

                    -  Disease with blast crisis that has entered into a second chronic phase after
                       induction chemotherapy

               -  Acute myelogenous leukemia meeting the following criteria:

                    -  Marrow blasts < 5% but persistence of minimal residual disease by flow
                       cytometry, cytogenetics, or FISH

                    -  Must meet one of the following criteria:

                         -  Disease in second or subsequent complete remission

                         -  Primary induction chemotherapy failure with disease subsequently
                            entering complete remission

                         -  Disease in first complete remission with poor-risk cytogenetics or
                            arising from preceding hematological disease

               -  Myelodysplastic syndrome meeting at least one of the following criteria:

                    -  Treatment-related

                    -  Monosomy 7 or complex cytogenetics

                    -  International prognostic scoring system score ≥ 1.5

                    -  Chronic myelomonocytic leukemia

               -  Acute lymphocytic leukemia or lymphoblastic lymphoma meeting the following
                  criteria:

                    -  Marrow blasts < 5% but persistence of minimal residual disease by flow
                       cytometry, cytogenetics, or FISH

                    -  Must meet one of the following criteria:

                         -  Disease in second or subsequent complete remission

                         -  Acute lymphocytic leukemia with poor-risk karyotype [e.g., t(9;22) or
                            bcr-abl fusion, t(4;11), or other MLL translocation] and in first
                            complete remission

               -  Chronic lymphocytic leukemia or prolymphocytic leukemia meeting both of the
                  following criteria:

                    -  Previously treated disease that has either relapsed or failed to respond
                       adequately to conventional-dose therapy including purine analogs

                    -  In the opinion of the transplant physician, unlikely to benefit from reduced
                       intensity transplantation due to the presence of one or more high-risk
                       features (i.e., bulky tumor masses, B symptoms, and/or inadequate response
                       to salvage chemotherapy)

               -  Hodgkin or non-Hodgkin lymphoma (including low-grade, mantle cell, and
                  intermediate-grade/diffuse disease) meeting the following criteria:

                    -  Previously treated disease that has either relapsed or failed to respond
                       adequately to conventional-dose therapy or autologous transplantation

                    -  In the opinion of the transplant physician, unlikely to benefit from reduced
                       intensity transplantation due to the presence of one or more high-risk
                       features (i.e., bulky tumor masses, B symptoms, and/or inadequate response
                       to salvage chemotherapy) NOTE: A new classification scheme for adult
                       non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent"
                       or "aggressive" lymphoma will replace the former terminology of "low",
                       "intermediate", or "high" grade lymphoma. However, this protocol uses the
                       former terminology.

          -  No available matched related or unrelated donor OR a matched related or unrelated
             donor will not be available in the time frame necessary to perform a transplant

          -  Availability of a first-degree relative (parent, child, sibling) matched at 3/6-5/6
             loci (HLA-A, -B, -DR)

               -  Donor must be willing to donate mobilized peripheral blood stem cells

               -  No positive HLA crossmatch in the host-vs-graft direction or high titer
                  donor-specific antibodies

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status 70-100%

          -  Bilirubin < 2 mg/dL (unless due to hemolysis, Gilbert syndrome, or primary malignancy)

          -  Creatinine < 2 mg/dL OR creatinine clearance ≥ 40 mL/min

          -  Not pregnant

          -  Fertile patients must use effective contraception

          -  LVEF (Left ventriculr ejection fraction) ≥ 45%

          -  FEV_1 and forced vital capacity ≥ 50% predicted

          -  No HIV positivity

          -  No debilitating medical or psychiatric illness that would preclude giving informed
             consent or receiving optimal treatment and follow-up

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No immunosuppressive agents ≤ 24 hours after completion of post-transplant
             cyclophosphamide (including steroids as antiemetics)