Study of Rasburicase as Treatment or Prevention of Hyperuricemia Associated With Tumor Lysis Syndrome in Patients With Relapsed or Refractory Lymphoma, Leukemia, or Solid Tumor Malignancy

This is a multi-center, 2 arm, open-label study;

• Arm A: Patients previously treated with a uricolytic agent;
• Arm B: Patients not previously treated with a uricolytic agent.

Patients receive rasburicase for 5 days and begin chemotherapy 4-24 hours after the first dose of rasburicase. Patients are followed at 14 and 35 days, at 3 and 6 months and every 6 months thereafter.

Inclusion criteria

• Meets one of the following risk criteria 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 a 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, refractory anemia with excess blast in transformation, or chronic myelomonocytic leukemia) only if they have > 10% bone marrow blast and are given aggressive treatment similar to AML

A patient is at potential risk for TLS if he/she presents with:

• A diagnosis of an 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 1 lymph node/tumor > 5 cm in diameter
• Patients previously treated with a uricolytic agent or not at their first relapse or refractory disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3. ECOG equivalent derived from Karnofsky performance scale 100-30 or Lansky performance score 100-30 (patients < or = 16 years of age) may also be used.
• Life expectancy >3 months
• Negative pregnancy test (females of child bearing potential) and use of effective contraceptive method (both males and females). A pregnancy test may be performed on serum or urine human chorionic gonadotropin (HCG).
• Signed written informed consent

Exclusion criteria

• History of established diagnosis of asthma or severe life-threatening atopic allergy
• Hypersensitivity to uricases or any of the excipients
• Known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency or history of hemolysis indicative of G6PD deficiency
• Pregnant or lactating
• Concomitant treatment with any investigational drug
• Planned treatment with rituximab
• Receipt of rituximab within the 12 month period prior to study entry
• Unwilling or unable to comply with the requirements of the protocol