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

Condition(s) targeted: Tumor Lysis Syndrome; Cancer; Hyperuricemia

Intervention: rasburicase (Drug); allopurinol (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: Sanofi-Aventis

Official(s) and/or principal investigator(s):
ICD, Study Director, Affiliation: Sanofi-Aventis

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

- rasburicase alone,

- rasburicase followed by allopurinol, and

- 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.

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

Study design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment

Primary outcome: Success/failure based on uric acid values

Secondary outcome:

uric acid AUC

Adverse events and laboratory data

Detailed description: This is a multi-center, open-label, randomized, parallel group study. After signing the informed consent and having met the inclusion criteria, patients will be randomized to 1 of the 3 following arms and treated for a total duration of 5 days: Arm A: The patient will receive 5 days of rasburicase treatment; Arm B: The patient will receive rasburicase from Day 1 through Day 3 and oral allopurinol from Day 3 through Day 5 (Day 3 is an overlap); Arm C: The patients will receive single agent oral allopurinol for 5 days. Patients in all groups will also receive chemotherapy beginning 4-24 hours after the first dose of rasburicase or allopurinol. Patients will be evaluated at 14 days, 35 days, at 3 months, 6 months and then every 6 months thereafter.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Alta Bates Comprehensive Cancer Center, Berkley, California 94704, United States

Rocky Mountain Cancer Center, Denver, Colorado 80218, United States

University of Florida Health Science Center at Jacksonville, Jacksonville, Florida 32209, United States

New York Medical College, Valhalla, New York 10595, United States

University of Pennsylvania Health Systems, Philadelphia, Pennsylvania 19104, United States

Mary Babb Randolph Cancer Center, Morgantown, West Virginia 26506-9162, United States

Starting date: April 2004
Ending date: July 2008
Last updated: June 2, 2008