Study of Rasburicase Versus Allopurinol in Patients With Leukemia, Lymphoma, or Solid Tumor Malignancy at Risk for Hyperuricemia and Tumor Lysis Syndrome - Full Text View

Sponsor:	Sanofi-Aventis
Information provided by:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00230178

Purpose

This is a randomized, multi-center, open-label, parallel group study with three arms:

Rasburicase alone
Rasburicase followed by Allopurinol
Allopurinol alone

The primary objective is to compare the adequacy of control of plasma uric acid concentration and the safety profile among the three arms.

Condition	Intervention	Phase
Tumor Lysis Syndrome Cancer Hyperuricemia	Drug: Rasburicase Drug: Allopurinol	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Evaluation of Single Agent Rasburicase for 5 Days Versus Sequential Treatment With Rasburicase From Day 1 Through 3 Followed by Oral Allopurinol From Day 3 Through 5 (Overlap on Day 3) Versus Single Agent Oral Allopurinol for 5 Days in the Management of Plasma Uric Acid in Adult Patients With Leukemia, Lymphoma, and Solid Tumor Malignancies at Risk for Hyperuricemia and Tumor Lysis Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Allopurinol sodium Rasburicase Allopurinol

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome Measures:

Success/failure based on uric acid values [ Time Frame: until 48 hours after the 5th day of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Uric acid AUC [ Time Frame: baseline to 48 hours after treatment stop ] [ Designated as safety issue: No ]
Adverse events and laboratory data [ Time Frame: study period ] [ Designated as safety issue: Yes ]

Enrollment:	280
Study Start Date:	April 2004
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A: Experimental Rasburicase alone given as a single agent for 5 days	Drug: Rasburicase 30-min IV infusion
Arm B: Experimental Rasburicase alone given as a single agent from Day 1 through Day 3, followed by oral allopurinol given from Day 3 through Day 5 (Day 3 is an overlap)	Drug: Rasburicase 30-min IV infusion Drug: Allopurinol Oral administration
Arm C: Active Comparator Oral allopurinol alone given as a single agent for 5 days	Drug: Allopurinol Oral administration

Detailed Description:

After signing the informed consent and having met the inclusion criteria, patients will be randomized to 1 of the 3 arms and treated for a total duration of 5 days. Patients in all arms will receive chemotherapy beginning 4-24 hours after the first dose of rasburicase or allopurinol.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Meets high risk or at potential risk for tumor lysis syndrome (TLS):

A patient is at high risk for TLS if he/she presents with:
- Hyperuricemia of malignancy (plasma uric acid > 7.5 mg/dL);
- A diagnosis of very aggressive lymphoma/leukemia based on the Revised European-American Lymphoma (REAL) classification of lymphoma/leukemia;
- Acute myeloid leukemia (AML);
- Chronic myeloid leukemia (CML) in blast crisis; or
- High grade myelodysplastic syndrome (refractory anemia with excess blast, chronic myelomonocytic leukemia, and refractory anemia with excess blast in transformation) only if they have > 10% bone marrow blast involvement and are given aggressive treatment similar to AML.
A patient is at potential risk for TLS if he/she presents with:
- A diagnosis of aggressive lymphoma/leukemia based on the REAL classification of lymphoma/leukemia plus 1 or more of the following criteria:
  - Lactate dehydrogenase (LDH) >= 2 x upper limit of normal (ULN) (IU/L)
  - Stage III-IV disease
  - Stage I-II disease with at least 1 lymph node/tumor > 5 cm in diameter
In addition to the above-mentioned eligibility criteria, the patients should have the following criteria:
Eastern Cooperative Oncology Group (ECOG) performance status 0-3
Age >= 18 years
Life expectancy > 3 months
Negative pregnancy test (females of child bearing potential) and use of effective contraceptive method (for both males and females). A pregnancy test may be performed on serum or urine human chorionic gonadotropin (HCG).
Signed written informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00230178

Locations

United States, California
Alta Bates Comprehensive Cancer Center
Berkley, California, United States, 94704
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
University of Florida Health Science Center at Jacksonville
Jacksonville, Florida, United States, 32209
United States, New York
New York Medical College
Valhalla, New York, United States, 10595
United States, Pennsylvania
University of Pennsylvania Health Systems
Philadelphia, Pennsylvania, United States, 19104
United States, West Virginia
Mary Babb Randolph Cancer Center
Morgantown, West Virginia, United States, 26506-9162

Sponsors and Collaborators

Sanofi-Aventis

Investigators

Study Director:

ICD

Sanofi-Aventis

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	sanofi-aventis ( ICD Study Director )
Study ID Numbers:	EFC4978, SR29142
Study First Received:	September 28, 2005
Last Updated:	August 27, 2008
ClinicalTrials.gov Identifier:	NCT00230178 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Sanofi-Aventis:

Hyperuricemia
Tumor lysis syndrome
Leukemia
Lymphoma

Myelodysplastic Syndromes
Solid tumor cancers
Solid Tumor cancers with hyperuricemia Hyperuricemia (cancer patients only)
Tumor lysis syndrome (cancer patients only)

Additional relevant MeSH terms:

Antimetabolites
Allopurinol
Antioxidants
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Gout Suppressants
Leukemia
Pathologic Processes
Syndrome
Therapeutic Uses
Free Radical Scavengers
Lymphoma
Disease

Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Hyperuricemia
Enzyme Inhibitors
Rasburicase
Protective Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Tumor Lysis Syndrome
Lymphoproliferative Disorders
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 27, 2009