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Rasburicase to Prevent Graft -Versus-Host Disease
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.
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.
Age
18 - 65 years
Sex
ALL
Healthy Volunteers
No
Massachusetts General Hospital
Boston, Massachusetts, United States
Start Date
January 1, 2008
Primary Completion Date
February 12, 2013
Completion Date
February 12, 2013
Last Updated
May 25, 2017
46
ACTUAL participants
busulfan
DRUG
cyclophosphamide
DRUG
cyclosporin-A
DRUG
etoposide
DRUG
methotrexate
DRUG
rasburicase
DRUG
sirolimus
DRUG
tacrolimus
DRUG
allogeneic hematopoietic stem cell transplantation
PROCEDURE
peripheral blood stem cell transplantation
PROCEDURE
total-body irradiation
RADIATION
fludarabine
DRUG
allopurinol
DRUG
Lead Sponsor
Massachusetts General Hospital
Data Source & Attribution
This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.
Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.
Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.
View ClinicalTrials.gov Terms and ConditionsNCT06311227