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.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2007

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
  • 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

• Success/failure based on uric acid values
  • Time Frame: until 48 hours after the 5th day of treatment
    Safety Issue?: No

Secondary Measures

• Uric acid AUC
  • Time Frame: baseline to 48 hours after treatment stop
    Safety Issue?: No
• Adverse events and laboratory data
  • Time Frame: study period
    Safety Issue?: Yes

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 Sponsor: Sanofi-Aventis

Overall Clinical Trial Officials and Contacts

ICD Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on December 03, 2008

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