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

Phase 4

Completed

• Conditions: Tumors; Hyperuricemia; Tumor Lysis Syndrome

• Registration Number: NCT00230217
• Lead Sponsor: Sanofi

Brief Summary

This is an open-label, multi-center study with 2 arms. The primary objective is to assess the response to treatment with rasburicase in 2 populations of adult and pediatric patients with lymphoma/leukemia/solid tumor malignancies, those previously treated with a uricolytic agent, and those not previously treated with a uricolytic agent at their first relapse or refractory disease.

Detailed Description

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.

Study Timeline

• Study Start: 2004-03
• Study First Submitted: 2005-09-28
• Study First Submitted QC: 2005-09-28
• Study First Posted: 2005-09-30
• Primary Completion: 2006-07
• Study Completion: 2006-07
• Status Verified: 2009-03
• Last Update Submitted: 2009-03-27
• Last Update Posted: 2009-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 94

Inclusion Criteria

1. 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

2. Patients previously treated with a uricolytic agent or not at their first relapse or refractory disease

3. 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.

4. Life expectancy >3 months

5. 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).

6. Signed written informed consent

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Positive response based on plasma uric acid levels.	up to 48 hours after last administration.

Secondary Outcome Measures

Name	Time	Method
safety assessment

Trial Locations

Locations (7)

Alta Bates Comprehensive Cancer Center; 🇺🇸 Berkley, California, United States

University of Florida Health Science Center at Jacksonville; 🇺🇸 Jacksonville, Florida, United States

University of Pennsylvania Health Systems; 🇺🇸 Philadelphia, Pennsylvania, United States

Rocky Mountain Cancer Center; 🇺🇸 Denver, Colorado, United States

New York Medical College; 🇺🇸 Valhalla, New York, United States

University of Oklahoma HSC; 🇺🇸 Oklahoma City, Oklahoma, United States

Mary Babb Randolph Cancer Center; 🇺🇸 Morgantown, West Virginia, United States