Rasburicase Versus Allopurinol in Tumor Patients at Risk for Hyperuricemia and Tumor Lysis Syndrome

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”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Rasburicase (SR29142)
  • 30-min IV infusion
• Drug: Allopurinol
  • Oral administration

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm A
  • Rasburicase alone given as a single agent for 5 days
• Experimental: Arm B
  • 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)
• Active Comparator: Arm C
  • Oral allopurinol alone given as a single agent for 5 days

Primary Measures

• Plasma Uric Acid Responder
  • Time Frame: Day 3 through Day 7
    Safety Issue?: No

Secondary Measures

• Plasma Uric Acid
  • Time Frame: Day 1 to Day 7
    Safety Issue?: No
• Time to Uric Acid Control
  • Time Frame: Day 1 to Day 7
    Safety Issue?: No

Inclusion Criteria:

• 1. 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:
• 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
• 3. Age >= 18 years
• 4. Life expectancy > 3 months
• 5. 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).
• 6. Signed written informed consent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sanofi-Aventis Industry

Overall Clinical Trial Officials and Contacts

International Clinical Development Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00230178

Study ID Number: EFC4978

ClinicalTrials.gov Identifier: NCT00230178

Health Authority: United States: Food and Drug Administration