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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2008 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00513474
First received: August 6, 2007
Last updated: February 16, 2012
Last verified: April 2008
  Purpose

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.


Condition Intervention
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: etoposide
Drug: methotrexate
Drug: rasburicase
Drug: sirolimus
Drug: tacrolimus
Other: diagnostic laboratory biomarker analysis
Other: flow cytometry
Other: immunologic technique
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Rasburicase to Prevent Graft -Versus-Host Disease

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphoma, Small Cleaved-cell, Diffuse Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Multiple Myeloma Chronic Myeloproliferative Disorders Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Homologous Wasting Disease Myelodysplastic/myeloproliferative Disease Acute Myeloid Leukemia, Adult Follicular Lymphoma B-cell Lymphomas Myelofibrosis Burkitt Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Hypereosinophilic Syndrome Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Leukemia, T-cell, Chronic Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Anaplastic Plasmacytoma
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence and severity of acute graft-vs-host disease

Secondary Outcome Measures:
  • Efficacy (in terms of reduction of uric acid levels) and safety
  • Graft-versus-host and host-versus-graft immune responses

Estimated Enrollment: 25
Study Start Date: January 2008
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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00513474

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114-2617
Contact: Bimalangshu R. Dey, MD, PhD    617-724-5255    BDEY@partners.org   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Bimalangshu R. Dey, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00513474     History of Changes
Other Study ID Numbers: CDR0000558480, MGH-07-071, DFCI-07-071
Study First Received: August 6, 2007
Last Updated: February 16, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
myelodysplastic/myeloproliferative neoplasm, unclassifiable
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)

Additional relevant MeSH terms:
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Graft vs Host Disease
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Immune System Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Busulfan
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate

ClinicalTrials.gov processed this record on April 15, 2014