Trials / Completed

CompletedNCT00513474

Rasburicase in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer or Other Disease Undergoing Donor Stem Cell Transplant

Rasburicase to Prevent Graft -Versus-Host Disease

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 46 (actual)

Sponsor: Massachusetts General Hospital · Academic / Other
Sex: All
Age: 18 Years – 65 Years
Healthy volunteers: Not accepted

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.

Conditions

Interventions

Type	Name	Description
DRUG	busulfan	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
DRUG	cyclophosphamide	Cyclophosphamide as standard of care for myeloablative conditioning at the investigator's discretion
DRUG	cyclosporin-A	Cyclosporin-A as standard of care for GVHD prophylaxis at the investigator's discretion
DRUG	etoposide	Etoposide as standard of care for myeloablative conditioning at the investigator's discretion
DRUG	methotrexate	Methotrexate 1.5 mg/kg/day on days -3, -2, and -1 as standard of care for GVHD prophylaxis at the investigator's discretion
DRUG	rasburicase	Rasburicase 0.20 mg/kg intravenous infusion over 30 minutes for 5 to 7 days
DRUG	sirolimus	Sirolimus as standard of care for GVHD prophylaxis at the investigator's discretion
DRUG	tacrolimus	Tacrolimus as standard of care for GVHD prophylaxis at the investigator's discretion
PROCEDURE	allogeneic hematopoietic stem cell transplantation
PROCEDURE	peripheral blood stem cell transplantation
RADIATION	total-body irradiation	Total body irradiation 13.2 Gy over 8 fractions from day -7 to day - 4 for myeloablative conditioning at the investigator's discretion
DRUG	fludarabine	Fludarabine 40 mg/m\^2/day from day -6 to day -3 as myeloablative conditioning at the investigator's discretion
DRUG	allopurinol	Allopurinol per institutional guidelines

Timeline

Start date: 2008-01-01
Primary completion: 2013-02-12
Completion: 2013-02-12
First posted: 2007-08-08
Last updated: 2017-05-25
Results posted: 2017-04-11

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00513474. Inclusion in this directory is not an endorsement.