Rasburicase in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer or Other Disease Undergoing Donor Stem Cell Transplant
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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.
Full 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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
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Patients with hematologic malignancies for whom conventional myeloablative allogeneic stem cell transplantation is deemed clinically appropriate and who are eligible for conventional myeloablative allogeneic stem cell transplantation on treatment plans/protocols, including any of the following:
- Non-Hodgkin lymphoma or Hodgkin lymphoma (relapsed or refractory disease)
- Chronic lymphocytic leukemia (received more than one previous treatment regimen)
- Acute myelogenous or lymphoblastic leukemia (AML/ALL) (high-risk disease, in first complete remission [CR1] or subsequent remission, or primary refractory disease)
- Chronic myelogenous leukemia in tyrosine-kinase resistant chronic phase, accelerated or blast phase, or primary refractory disease
- Myelodysplastic syndromes in International Prognostic Scoring System (IPSS) high-intermediate or high-risk groups
- Other hematologic disorders for which allogeneic stem cell transplantation is appropriate (e.g., myelofibrosis)
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Patients who have relapsed after standard autologous and/or allogeneic bone marrow transplant are eligible
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Must be receiving filgrastim (G-CSF)-mobilized related or unrelated donor allogeneic peripheral blood stem cells
- Patients receiving hematopoietic stem cells of any other sources such as a marrow graft or umbilical cord blood will not be eligible for this study
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Donor must be HLA-genotypically or phenotypically 6 of 6 antigen matched (at the A, B, DR loci) related or unrelated
PATIENT CHARACTERISTICS:
Inclusion criteria:
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Patients with a "currently active" second malignancy other than non-melanoma skin cancers can only be registered if survival from the second malignancy is expected to be more than 1 year
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Ejection fraction ≥ 45% by either radioisotope Multiple Gated Acquisition Scan (MUGA) scan or Echocardiogram (ECHO)
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Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) ≥ 50% of predicted with no symptomatic pulmonary disease
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Mini Mental Status Exam Score ≥ 20
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Patients must have an expected life expectancy of at least 3 months
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Patients with symptomatic visceral, blood stream or nervous system opportunistic infection are eligible if the infection has been appropriately treated and controlled
- Patients with a fungal infection must have had treatment for at least one month and must have proof of regression of the infection prior to enrollment
- Patients may be on antibiotics at the time of transplant
Exclusion criteria:
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Human Immunodeficiency Virus (HIV) infection
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Uncontrolled diabetes mellitus
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Active congestive heart failure from any cause
- Previous history of congestive heart failure allowed
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Active angina pectoris
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Oxygen-dependent obstructive pulmonary disease
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Failure to demonstrate adequate compliance with medical therapy and follow-up
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Known history of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency or history of hemolysis indicative of G6PD deficiency
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial design
Primary purpose
Allocation
Interventional model
Masking
46 participants in 2 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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