Clinical trial NCT00513474
Conditions: Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms
Keywords: graft versus host disease anaplastic large cell lymphoma angioimmunoblastic T-cell lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma recurrent adult Burkitt 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 adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult T-cell leukemia/lymphoma recurrent cutaneous T-cell non-Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent mycosis fungoides/Sezary syndrome recurrent small lymphocytic lymphoma splenic marginal zone lymphoma Waldenström macroglobulinemia recurrent adult acute lymphoblastic leukemia refractory chronic lymphocytic leukemia recurrent adult acute myeloid leukemia 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) accelerated phase chronic myelogenous leukemia blastic phase chronic myelogenous leukemia chronic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia previously treated myelodysplastic syndromes primary myelofibrosis atypical chronic myeloid leukemia, BCR-ABL1 negative chronic eosinophilic leukemia chronic myelomonocytic leukemia de novo myelodysplastic syndromes myelodysplastic/myeloproliferative neoplasm, unclassifiable refractory hairy cell leukemia refractory multiple myeloma secondary acute myeloid leukemia secondary myelodysplastic syndromes
Sponsor: Massachusetts General Hospital
Start date: 2008-01-01; Completion date: 2013-02-12
Enrollment: 46 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Rasburicase may be an effective treatment for graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This clinical trial is studying how well rasburicase works in preventing graft-versus-host disease in patients with hematologic cancer or other disease undergoing donor stem cell transplant.

Detailed description:
OBJECTIVES:

Primary

* To evaluate the incidence and severity of acute graft-vs-host disease (GVHD) in rasburicase-treated patients who will undergo myeloablative human leukocyte antigen (HLA)-matched related or unrelated donor allogeneic peripheral blood hematopoietic stem cell transplantation (SCT) for hematologic malignancies and compare these outcomes with those of historical controls.

Secondary

* To evaluate the efficacy (in terms of reduction of uric acid levels) and safety of rasburicase in patients undergoing myeloablative allogeneic SCT.
* To evaluate the graft-versus-host and host-versus-graft immune responses in rasburicase-treated patients.

OUTLINE: This is a multicenter study.

Patients receive a conventional myeloablative conditioning regimen consisting of high doses of cyclophosphamide, busulfan, and etoposide, with or without total-body irradiation. Depending on the preparative regimen selected, the conditioning of recipients will take a total of 6 to 7 days. On day 0, patients will receive filgrastim (G-CSF)-mobilized HLA-matched, related, or unrelated donor allogeneic peripheral blood stem cells (unmanipulated). Patients will receive standard graft-vs-host disease prophylaxis consisting of cyclosporine or tacrolimus and methotrexate or sirolimus. Patients will receive rasburicase IV over 30 minutes, beginning on the first day of conditioning therapy, for 5 consecutive days. If after 5 days of rasburicase the patient's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total.

Blood is obtained on day 0 and then at 14, 28, and 42 days post-transplant for immunologic studies, including quantitative analysis to follow the recovery of T cells, B cells, natural killer cells, dendritic cells (DC), and monocytes using flow cytometry (FCM); phenotypic analysis of T cells, DC and monocytes by FCM; lymphocyte activation analysis: CD3, CD4, CD8, CD25 2. CD3, CD8, CD71, CD69; DC analysis: CD45, CD14, DR, CD86, CD80 2. CD45, CD14, CD40, CD11c; and in vitro functional studies such as mixed lymphocyte reaction (MLR) and cell-mediated lysis (CML) to assess for the graft-versus-host and host-versus-graft responses. Peripheral blood is collected for chimerism studies on days 28 and 100 post-transplant.

After completion of study treatment, patients are followed periodically.

Arms: arm 1: Myeloablative (bone marrow depletion) conditioning protocol as per standard of care at the investigator's discretion followed by granulocyte colony-stimulating factor (GCSF)-mobilized human leukocyte antigen (HLA)-matched, related or unrelated donor allogeneic peripheral blood stem cells (unmanipulated), standard graft-versus-host disease (GVHD) prophylaxis as per standard of care at the investigator's discretion and rasburicase 0.20 mg/kg/day administered by intravenous infusion for 5 consecutive days. If after 5 days of rasburicase the participant's uric acid plasma level remains above 5 mg/dL, rasburicase may be continued for up to 7 days in total. arm 2: Historical chart review of patients from the Blood and Marrow Transplant database who received myeloablative allogeneic stem cell/bone marrow transplantation followed by standard GVHD prophylaxis in the past 10 years. Participants received allopurinol per institutional guidelines.
Interventions: intervention 1: busulfan intervention 2: cyclophosphamide intervention 3: cyclosporin-A intervention 4: etoposide intervention 5: methotrexate intervention 6: rasburicase intervention 7: sirolimus intervention 8: tacrolimus intervention 9: allogeneic hematopoietic stem cell transplantation intervention 10: peripheral blood stem cell transplantation intervention 11: total-body irradiation intervention 12: fludarabine intervention 13: allopurinol
Intervention descriptions: intervention 1: Busulfan 3.2 mg/kg/day from day -7 to day -4 as standard of care for myeloablative (bone marrow depletion) conditioning at the investigator's discretion intervention 2: Cyclophosphamide as standard of care for myeloablative conditioning at the investigator's discretion intervention 3: Cyclosporin-A as standard of care for GVHD prophylaxis at the investigator's discretion intervention 4: Etoposide as standard of care for myeloablative conditioning at the investigator's discretion intervention 5: Methotrexate 1.5 mg/kg/day on days -3, -2, and -1 as standard of care for GVHD prophylaxis at the investigator's discretion intervention 6: Rasburicase 0.20 mg/kg intravenous infusion over 30 minutes for 5 to 7 days intervention 7: Sirolimus as standard of care for GVHD prophylaxis at the investigator's discretion intervention 8: Tacrolimus as standard of care for GVHD prophylaxis at the investigator's discretion intervention 9: None intervention 10: None intervention 11: Total body irradiation 13.2 Gy over 8 fractions from day -7 to day - 4 for myeloablative conditioning at the investigator's discretion intervention 12: Fludarabine 40 mg/m\^2/day from day -6 to day -3 as myeloablative conditioning at the investigator's discretion intervention 13: Allopurinol per institutional guidelines

Protocol documents: