Donor Stem Cell Transplant, Pentostatin, and Total-Body Irradiation in Treating Patients With Hematological Cancer
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
About this trial
This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring 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 myeloid leukemia in remission, recurrent adult acute myeloid leukemia, secondary acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, essential thrombocythemia, polycythemia vera, primary myelofibrosis, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, marginal zone B-cell lymphoma of mucosal lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, aplastic anemia, chronic eosinophilic leukemia, chronic neutrophilic leukemia, contiguous st II adult diffuse small cleaved cell lymphoma, noncontig stage II adult diffuse small cleaved cell lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, stage I marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage I mantle cell lymphoma, contiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, stage I adult lymphoblastic lymphoma, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of a confirmed hematological malignancy that has relapsed or is at high risk for relapsing, including any of the following:
Acute myeloid leukemia (AML) meeting any of the following criteria:
- Antecedent hematologic disorder
- Therapy related
- Primary induction failure
In first complete remission (CR1) with poor-risk cytogenetics, as defined by the following:
- del(5q)/-5
- del(7q)/-7
- abn(3q)
- t(6;9)
- del(20q)
- del(17p)
- +13
- Complex karyotype
- t(9;22) = 11q23 rearrangement
- In second complete remission (CR2) or greater
Acute lymphoblastic leukemia meeting any of the following criteria:
- In CR1 with WBC > 50,000/mm³ at diagnosis
- In CR1 with poor-risk cytogenetics (i.e., t[9;22], t[1;19], t[4;11]) AND meets at least 1 of the following criteria:
= 19-75 years of age AND received prior high-dose chemotherapy, total-body irradiation (TBI), or a radiation dose that precludes administration of 12 Gy of TBI = 50-75 years of age = 19-75 years of age with hematopoietic stem cell transplantation (HSCT) comorbidity index ≥ 3
- CNS or testicular involvement at diagnosis
- No CR within 4 weeks of initial treatment
- Primary induction failure
In CR2 or greater
- Myelodysplastic syndromes meeting the following criteria:
- Intermediate-2 or high-risk category as determined by International Prognostic Scoring System
Not considered a candidate for intensive or standard chemotherapy or HSCT
- Chronic myelogenous leukemia meeting any of the following criteria:
- First chronic phase AND < 40 years of age
- First chronic phase AND no hematologic response after 3 months of imatinib mesylate therapy
- First chronic phase AND never achieved a complete cytogenetic response during imatinib mesylate therapy
- First chronic phase AND loss of previously documented response
- Accelerated phase
Blast crisis phase
- Chronic myeloproliferative disorder (i.e., polycythemia vera, essential thrombocythemia, myelofibrosis)
Bone marrow blasts > 5% and/or other evidence of progression to acute leukemia
- Chronic myelomonocytic leukemia
- Severe aplastic anemia
Failed prior antithymocyte globulin and cyclosporine immunosuppressive therapy
- Mantle cell lymphoma meeting any of the following criteria:
- In CR1
- In first partial remission (PR1)
- In CR 2 or greater
In second PR (PR2) or greater
- Indolent non-Hodgkin lymphoma OR chronic lymphocytic leukemia meeting either of the following criteria:
- In CR 2 or greater
In PR 2 or greater
- Lymphoblastic lymphoma
In CR1 or greater
Must have minimal residual disease as defined by either of the following:
- No more than 5% blasts in blood and/or bone marrow (in patients with acute leukemia/MDS)
- No bulky adenopathy (> 5 cm masses) and/or < 20% bone marrow involvement by lymphoma (in patients with lymphoma)
- No progressive disease within 8 weeks of most recent prior therapy OR within 12 weeks of prior autologous HSCT
- No active CNS malignancy (i.e., known positive CSF cytology or parenchymal lesions visible by CT scan or MRI)
HLA-matched unrelated peripheral blood stem cell donor available
- Meets the University of Nebraska Medical Center's or the National Marrow Donor Program's criteria for donors
- Matched at 7/8 or 8/8 HLA-A, B, C, or DRβ1 loci by molecular typing
If match is not at allele level, suitability for donation requires discussion with and approval by the principal investigator
- Not an identical twin
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Creatinine clearance ≥ 55 mL/min
- Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert's disease or malignancy)
- ALT and AST ≤ 4 times ULN
- DLCO ≥ 40%
- FEV1/FVC ratio ≥ 50% of predicted
- Cardiac ejection fraction ≥ 40%
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Not receiving supplementary continuous oxygen
- No NYHA grade II-IV cardiac disease
- HIV negative
- No evidence of active hepatitis B (i.e., positive HBsAg and/or positive HBeAg or high copy number on quantitative RNA testing) or hepatitis C
- No active uncontrolled infection or immediate life-threatening condition
- No uncontrolled medical illnesses (e.g., uncontrolled systemic hypertension or diabetes)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior cytoreductive chemotherapy or irradiation to areas of bulky disease allowed, as determined by the primary physician in consultation with the study investigators
- No other concurrent anti-tumor therapy
Sites / Locations
Arms of the Study
Arm 1
Experimental
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer
This phase I/II trial is studying the side effects of giving a donor stem cell transplant after pentostatin and total-body irradiation and to see how well it works in treating patients with hematological cancer.