Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Rasburicase and/or Allopurinol in Controlling High Levels of Uric Acid in the Blood and Tumor Lysis Syndrome in Patients With Leukemia, Lymphoma, or Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase IV Supportive care Closed 18 and over Pharmaceutical / Industry PROLOGUE-EFC4978 UCLA-0403071-01, NCT00230178

Objectives

Primary

1. Compare the adequacy of plasma uric acid concentration control in patients with leukemia, lymphoma, or solid tumor malignancy at risk for hyperuricemia and tumor lysis syndrome treated with rasburicase alone vs rasburicase and allopurinol vs allopurinol alone.

Secondary

1. Compare plasma uric acid area under the curve from within 4 hours before first treatment through 48 hours after the last treatment with these regimens in these patients.
2. Determine the incidence, duration, and type of immune responses (immunoglobulin [Ig]G, IgE, and neutralizing antibody) in patients treated with rasburicase.
3. Determine the efficacy and safety of rasburicase, in terms of antibody generation and antibody titer, in these patients.

Entry Criteria

Disease Characteristics:

• Meets 1 of the following risk criteria for tumor lysis syndrome:
  • At high-risk, with any of the following diagnoses:
    • Hyperuricemia of malignancy (plasma uric acid > 7.5 mg/dL)
    • Very aggressive lymphoma or leukemia
    • Acute myeloid leukemia (AML)
    • Chronic myelogenous leukemia in blast crisis
    • High-grade myelodysplastic syndromes (refractory anemia with excess blasts [RAEB], chronic myelomonocytic leukemia, or RAEB in transformation) AND ≥ 10% bone marrow blast involvement AND receiving aggressive treatment similar to AML
  • At potential-risk AND a diagnosis of aggressive lymphoma or leukemia AND meets at least one of the following criteria:
    • Lactic dehydrogenase ≥ 2 times upper limit of normal
    • Stage III or IV disease
    • Stage I or II disease with at least 1 lymph node or tumor measuring > 5 cm in diameter



• No relapsed or refractory leukemia, lymphoma, or solid tumor

Prior/Concurrent Therapy:

Biologic therapy

• Concurrent rituximab allowed

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior uricolytic therapy (e.g., rasburicase or nonrecombinant urate oxidase [Uricozyme®])
• No other concurrent investigational drug
• No other concurrent hyperuricemic agent

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-3

Life expectancy

• More than 3 months

Hematopoietic

• No history of hemolysis indicative of G6PD deficiency

Hepatic

• See Disease Characteristics

Renal

• Not specified

Pulmonary

• No established diagnosis of asthma

Other

• No severe, life-threatening atopic allergy
• No hypersensitivity attributed to uricases or any of their excipients
• No known G6PD deficiency
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 30 days after study participation

Expected Enrollment

A total of 276 patients (92 per treatment arm) will be accrued for this study within 25 months.

Outcomes

Plasma uric acid concentration measured by the area under the curve (AUC) at baseline through 48 hours after the last dose of chemotherapy
Safety profile as measured by laboratory tests and adverse events at baseline through day 35

Immune response to rasburicase as measured by plasma immunoassay (IgG, IgE, and neutralizing antibody) at baseline through 6 months after treatment or until negative after 6 months
Pharmacokinetics of rasburicase as measured by plasma levels at baseline through day 14

Outline

This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to risk for tumor lysis syndrome (high risk vs potential risk). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive rasburicase IV over 30 minutes on days 1-5.



• Arm II: Patients receive rasburicase IV over 30 minutes on days 1-3 and oral allopurinol once daily on days 3-5.



• Arm III: Patients receive oral allopurinol once daily on days 1-5.

In all arms, treatment continues in the absence of unacceptable toxicity.

All patients receive cytoreductive chemotherapy off-study beginning 4-24 hours after the first dose of rasburicase and/or allopurinol.

Patients are followed at 14 days after the first dose of study treatment). After completion of study treatment, patients are followed at 30 days, at 3 and 6 months, and then every 6 months thereafter.

Trial Contact Information

Trial Lead Organizations

Prologue Research International, Incorporated

Richard Gams, MD, Protocol chair		Ph: 614-324-1500; 800-906-6565

Registry Information
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
Registered in ClinicalTrials.gov		NCT00230178
Date Submitted to PDQ		2004-05-17
Information Last Verified		2008-01-09