Alemtuzumab Plus Fludarabine and Melphalan With or Without Cyclosporine, Mycophenolate Mofetil, and Low-Dose Total-Body Irradiation Therapy Followed by Donor Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
About this trial
This is an interventional treatment trial for Leukemia focused on measuring recurrent adult acute myeloid leukemia, adult acute myeloid leukemia in remission, recurrent adult acute lymphoblastic leukemia, adult acute lymphoblastic leukemia in remission, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic myelomonocytic leukemia, recurrent adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, recurrent mantle cell lymphoma, recurrent adult lymphoblastic lymphoma, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, refractory multiple myeloma, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes, 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)
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed hematological malignancy of 1 of the following types: Acute myeloid leukemia meeting at least 1 of the following criteria: Poor-risk cytogenetics, including -5, 5q-, -7, 7q-, 11q23, and Philadelphia (Ph) chromosome-positive in first or subsequent complete remission (CR) Relapsed or primary refractory disease with ≤ 10% blasts in the peripheral blood and ≤ 20% blasts in the bone marrow Standard-risk cytogenetics in second CR AND autologous transplantation is not feasible Standard-risk cytogenetics in third or subsequent CR Acute lymphoblastic leukemia meeting 1 of the following criteria: Second or subsequent CR High-risk cytogenetics, including Ph chromosome-positive and t(4:11) in first CR Relapsed or primarily refractory disease with ≤ 10% blasts in the peripheral blood and ≤ 20% blasts in the bone marrow High-risk myelodysplasia International Prognostic Scoring System Score ≥ 2.5 Chronic myeloid leukemia (CML)* with an inadequate response to imatinib meeting 1 of the following criteria: Second or subsequent chronic phase Accelerated phase NOTE: *Patients with CML in blast crisis (> 30% promyelocytes and myeloblasts in the bone marrow) are not eligible Non-Hodgkin's lymphoma meeting 1 of the following criteria: Primarily refractory disease or in refractory relapse Relapsed disease after autologous stem cell transplantation Chemosensitive relapsed disease without CR to standard salvage therapy AND no option for autologous stem cell transplantation due to blood or marrow involvement or failure to harvest sufficient autologous stem cells Chronic lymphocytic leukemia meeting both of the following criteria: Stage III or IV disease Refractory to fludarabine Multiple myeloma meeting 1 of the following criteria: Primarily refractory disease or in refractory relapse Relapsed disease after autologous stem cell transplantation No relapsed disease < 6 months after autologous stem cell transplantation No available eligible HLA-matched (i.e., 5 of 6 or 6 of 6 antigen match for HLA-A, -B, and -DR loci) family donor by serological or molecular typing Available suitable family donor meeting the following criteria: Parent, sibling, or child of the recipient ≥ 16 years of age Identical for only one HLA haplotype (i.e., haploidentical) AND incompatible at the HLA-A, -B, -C, and -DR loci of the unshared haplotype by serological or molecular typing Mismatched with respect to KIR class I epitopes graft-vs-host directional activity Mismatching that predicts both graft-vs-host and host-vs-graft bi-directional activity eligible No mismatching that predicts only host-vs-graft directional activity PATIENT CHARACTERISTICS: Age 18 to 60 Performance status ECOG 0-1 Hepatic Bilirubin < 2 times upper limit of normal (ULN) AST and ALT < 2 times ULN Renal Creatinine ≤ 2 mg/dL Cardiovascular LVEF > 40% (corrected) Pulmonary DLCO > 50% of predicted Other No active infection requiring oral or IV antibiotics HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy See Disease Characteristics Endocrine therapy Concurrent corticosteroids allowed for adrenal failure, treatment of graft-vs-host disease, or as premedication during study No concurrent corticosteroids for antiemesis
Sites / Locations
- Moores UCSD Cancer Center
- Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
- UCSF Comprehensive Cancer Center
- CCOP - Christiana Care Health Services
- Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
- University of Chicago Cancer Research Center
- Holden Comprehensive Cancer Center at University of Iowa
- Massachusetts General Hospital Cancer Center
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
- University of Minnesota Cancer Center
- Siteman Cancer Center at Barnes-Jewish Hospital
- UNMC Eppley Cancer Center at the University of Nebraska Medical Center
- St. Joseph's Hospital and Medical Center
- Roswell Park Cancer Institute
- Don Monti Comprehensive Cancer Center at North Shore University Hospital
- Memorial Sloan-Kettering Cancer Center
- Mount Sinai Medical Center
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
- Duke Comprehensive Cancer Center
- Wake Forest University Comprehensive Cancer Center
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
- Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
- Hollings Cancer Center at Medical University of South Carolina
- Virginia Commonwealth University Massey Cancer Center
Arms of the Study
Arm 1
Experimental
Regimen A + B
Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2. Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1. All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients are followed every 3 months for 1 year and then every 6 months for 5 years.