Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer
Leukemia, Lymphoma, Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Leukemia focused on measuring 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
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)
Sites / Locations
- Blood and Marrow Transplant Group of Georgia
Arms of the Study
Arm 1
Experimental
Myeloablative Haploidentical Transplant
All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.