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

Lymphoma Clinical Trial

Official title:

Rasburicase to Prevent Graft -Versus-Host Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00513474
• Other study ID #: CDR0000558480
• Secondary ID: MGH-07-071DFCI-0
• Status: Completed
• Phase: N/A
• First received: August 6, 2007
• Last updated: May 8, 2015
• Start date: January 2008
• Est. completion date: March 2013

Study information

• Verified date: May 2015
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• To evaluate the incidence and severity of acute graft-vs-host disease (GVHD) in rasburicase-treated patients who will undergo myeloablative 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS:

• 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 IPSS (International Prognostic Scoring System) high-intermediate or high-risk groups

• Other hematologic disorders for which allogeneic stem cell transplantation is appropriate (e.g., myelofibrosis)

• Patients who have relapsed after standard autologous and/or allogeneic bone marrow transplant are eligible

• 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

• 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:

• 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

• Ejection fraction = 45% by either radioisotope MUGA scan or ECHO

• Lung DLCO = 50% of predicted with no symptomatic pulmonary disease

• Mini Mental Status Exam Score = 20

• Patients must have an expected life expectancy of at least 3 months

• 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:

• HIV infection

• Uncontrolled diabetes mellitus

• Active congestive heart failure from any cause

• Previous history of congestive heart failure allowed

• Active angina pectoris

• Oxygen-dependent obstructive pulmonary disease

• Failure to demonstrate adequate compliance with medical therapy and follow-up

• Known history of G6PD deficiency or history of hemolysis indicative of G6PD deficiency

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Design

Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Neoplasms
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia

Intervention

Drug:
• busulfan

• cyclophosphamide

• cyclosporine

• etoposide

• methotrexate

• rasburicase

• sirolimus

• tacrolimus

Other:
• diagnostic laboratory biomarker analysis

• flow cytometry

• immunologic technique

Procedure:
• allogeneic hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Radiation:
• total-body irradiation

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of acute graft-vs-host disease
Secondary	Efficacy (in terms of reduction of uric acid levels) and safety
Secondary	Graft-versus-host and host-versus-graft immune responses