early administration of atg followed by cyclophosphamide, busulfan and fludarabine before a donor stem cell transplant in patients with hematological cancer

Conditions: Myeloproliferative Disorders; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Summary: rationale: giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. it may also stop the patient's immune system from rejecting the donor's stem cells. the donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. giving antithymocyte globulin before the transplant and tacrolimus and methotrexate after the transplant may stop this from happening. purpose: this phase ii trial is studying how well giving antithymocyte globulin together with cyclophosphamide, busulfan, and fludarabine works in treating patients with hematological cancer or kidney cancer undergoing donor stem cell transplant.

objectives: * to assess the percentage of patients with hematological malignancies or renal cell carcinoma who achieve \> 90% donor t-cell chimerism at 30 days after treatment with reduced-intensity conditioning comprising low-dose anti-thymocyte globulin, low-dose cyclophosphamide, busulfan, and fludarabine phosphate followed by allogeneic peripheral blood progenitor cell transplantation from a matched related donor. * to assess the incidence of severe (grade 3 or 4) acute graft-versus-host disease (gvhd) and extensive chronic gvhd in these patients. * to assess whether this regimen is associated with reduced transplant-related toxicity and increased tolerability in these patients. * to assess the overall safety of this conditioning regimen as measured by 6-month transplant-related mortality in these patients. * to determine the efficacy of this regimen in inducing durable remissions in these patients. outline: * reduced-intensity conditioning (ric): patients receive anti-thymocyte globulin iv over 4-6 hours on day -16 and over 6-8 hours on day -15, fludarabine phosphate iv over 30 minutes on days -7 to -3, busulfan iv over 3 hours on days -4 and -3, and cyclophosphamide iv over 1-2 hours on day -2. * transplantation: patients undergo allogeneic peripheral blood progenitor cell transplantation on day 0. * graft-vs-host disease (gvhd) prophylaxis: patients receive oral tacrolimus every 12 hours on days -1 to 90, followed by a taper until day 150. patients also receive methotrexate iv on days 1, 3, and 6. blood samples are collected periodically for pharmacokinetic studies of anti-thymocyte globulin and pcr analysis for chimerism. after completion of study therapy, patients are followed periodically for up to 3 years.

Eligibility criteria:
disease characteristics: * histologically confirmed diagnosis of one of the following: * chronic myeloid leukemia (cml) * philadelphia chromosome (ph)- and/or bcr-abl-positive disease * in chronic or accelerated phase * suboptimal response to imatinib mesylate (i.e., no hematologic complete response by 3 months, no major cytogenetic response by 6 months, or no complete cytogenetic response by 1 year) * cml in blastic transformation allowed provided patient achieved complete remission (cr) or second chronic phase after treatment with imatinib mesylate or chemotherapy * chronic lymphocytic leukemia meeting one of the following criteria: * rai stage iii or iv disease * rai stage i or ii disease that failed standard therapy (i.e., disease is progressing after ≥ 1 course of standard therapy) * non-hodgkin lymphoma (nhl) meeting one of the following criteria: * indolent nhl * clinical stage iii or iv disease or bulky stage ii disease (i.e., ≥ one lymphoid mass \> 5 cm in ≥ one dimension) * relapsed after primary therapy or is refractory to therapy * aggressive nhl * is not considered curable with standard chemotherapy or autologous stem cell transplantation (i.e., relapsed after autologous stem cell transplantation) * chemotherapy-responsive disease * multiple myeloma * durie-salmon stage ii or iii disease * durie salmon stage i disease allowed provided β2 microglobulin level \> 3 mg/dl * acute myeloid leukemia or acute lymphocytic leukemia * in cr (defined as \< 5% blasts in bone marrow and no circulating blasts) and has any of the following poor prognostic features: * wbc \> 100,000/mm\^3 at presentation * in second or greater remission * adverse-risk cytogenetics (i.e., ph1-positive, 11q23 translocation, -5, -7, complex translocations, or other recognized adverse-risk cytogenetics) * renal cell carcinoma * stage iv disease * clear cell morphology * myelodysplastic syndromes * bone marrow blasts ≤ 10% on last bone marrow biopsy prior to transplantation * myeloproliferative disease * anticipated life expectancy on conventional therapy \< 10 years * no uncomplicated essential thrombocythemia or primary polycythemia * hodgkin lymphoma * relapsed after ≥ 1 standard-dose chemotherapy regimen * not considered curable by autologous stem cell transplantation * no clinical evidence of active cns involvement * previously treated leptomeningeal disease allowed provided csf cytology is negative at the time of assessment for transplantation * available 6/6 allele match (i.e., hla-a, b, drβ1)matched related donor patient characteristics: * ecog performance status (ps) 0-2 or karnofsky ps 60-100% * bilirubin \< 3 times normal (unless abnormality due to malignancy) * ast and alt \< 3 times normal (unless abnormality due to malignancy) * creatinine ≤ 2.0 mg/dl * lvef ≥ 40% by muga or echo * dlco ≥ 40% of predicted * fev-1 ≥ 50% of predicted * not pregnant or nursing * fertile patients must use effective contraception * deemed to be an appropriate candidate for allogeneic sct * no evidence of myocardial infarction within the past 6 months * no psychological or social condition that may interfere with study participation * no serious uncontrolled localized or active systemic infection * no second malignancy within the past 3 years except for completely excised nonmelanotic skin cancer or in situ carcinoma of the cervix * no chronic inflammatory disorder requiring the continued use of glucocorticoids or other immunosuppressive medications * no known hiv positivity * no hypersensitivity to e. coli-derived proteins

Keywords: accelerated phase cml blastic phase cml philadelphia chromosome positive cml stage i cll stage ii cll stage iii cll stage iv cll stage i multiple myeloma stage ii multiple myeloma stage iii multiple myeloma adult aml with 11q23 (mll) abnormalities adult cml in remission adult all in remission stage iv renal cell cancer de novo mds previously treated mds secondary mds atypical cml, bcr-abl negative chronic myelomonocytic leukemia mds/myeloproliferative neoplasm, unclassifiable primary myelofibrosis chronic neutrophilic leukemia recurrent adult hodgkin lymphoma clear cell renal cell carcinoma adult aml with inv(16)(p13;q22) adult aml with t(15;17)(q22;q12) adult aml with t(16;16)(p13;q22) adult aml with t(8;21)(q22;q22) adult nasal type extranodal nk/t-cell lymphoma aml/transient myeloproliferative disorder burkitt lymphoma chronic phase cml extranodal marginal zone b-cell lymphoma of mucosa tissue nodal marginal zone b-cell lymphoma stage iii adult burkitt lymphoma stage iv adult burkitt lymphoma recurrent adult burkitt lymphoma stage iii adult diffuse large cell lymphoma stage iii adult diffuse mixed cell lymphoma recurrent adult diffuse large cell lymphoma stage iv adult diffuse large cell lymphoma stage iv adult diffuse mixed cell lymphoma recurrent adult diffuse mixed cell lymphoma stage iii adult immunoblastic large cell lymphoma stage iv adult immunoblastic large cell lymphoma stage iii adult lymphoblastic lymphoma stage iv adult lymphoblastic lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 3 follicular lymphoma stage iii grade 3 follicular lymphoma stage iv grade 3 follicular lymphoma recurrent mantle cell lymphoma stage iii mantle cell lymphoma stage iv mantle cell lymphoma contiguous st ii adult diffuse small cleaved cell lymphoma noncontiguous st ii diffuse small cleaved cell lymphoma recurrent 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 recurrent grade 1 follicular lymphoma recurrent 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 recurrent 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 recurrent small lymphocytic lymphoma stage iii small lymphocytic lymphoma stage iv small lymphocytic lymphoma recurrent adult grade iii lymphomatoid granulomatosis relapsing chronic myelogenous leukemia refractory chronic lymphocytic leukemia splenic marginal zone lymphoma waldenstrom macroglobulinemia recurrent adult t-cell leukemia/lymphoma stage iii adult t-cell leukemia/lymphoma stage iv adult t-cell leukemia/lymphoma anaplastic large cell lymphoma angioimmunoblastic t-cell lymphoma