Rasburicase in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer or Other Disease Undergoing Donor Stem Cell Transplant
Condition: Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Graft vs Host Disease; Syndrome
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): busulfan; cyclophosphamide; cyclosporin-A; etoposide; methotrexate; rasburicase; sirolimus; tacrolimus; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; total-body irradiation; fludarabine; allopurinol
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation; Drug; Drug
Intervention description(s): 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; Cyclophosphamide as standard of care for myeloablative conditioning at the investigator's discretion; Cyclosporin-A as standard of care for GVHD prophylaxis at the investigator's discretion; Etoposide as standard of care for myeloablative conditioning at the investigator's discretion; Methotrexate 1.5 mg/kg/day on days -3, -2, and -1 as standard of care for GVHD prophylaxis at the investigator's discretion; Rasburicase 0.20 mg/kg intravenous infusion over 30 minutes for 5 to 7 days; Sirolimus as standard of care for GVHD prophylaxis at the investigator's discretion; Tacrolimus as standard of care for GVHD prophylaxis at the investigator's discretion; Total body irradiation 13.2 Gy over 8 fractions from day -7 to day - 4 for myeloablative conditioning at the investigator's discretion; Fludarabine 40 mg/m^2/day from day -6 to day -3 as myeloablative conditioning at the investigator's discretion; Allopurinol per institutional guidelines
Intervention MeSH terms: Cyclosporine; Sirolimus; Cyclophosphamide; Busulfan; Methotrexate; Fludarabine; Etoposide; Allopurinol; Rasburicase; Tacrolimus; Cyclosporins
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
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