Rasburicase in Patients at Risk for Tumor Lysis Syndrome
Condition: Tumor Lysis Syndrome
MeSH terms: Tumor Lysis Syndrome; Syndrome
Intervention: As Needed Rasburicase; Fixed Dose Rasburicase
Intervention description: .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed.; .15 mg/kg IV Over 30 Minutes Daily
Intervention MeSH terms: Rasburicase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Healthy volunteers: No
Keywords: Tumor Lysis Syndrome; TLS; hyperuricemia; Leukemia; Lymphoma; Acute myeloid leukemia; Chronic myelocytic leukemia; CML; lactate dehydrogenase; LDH; Myelodysplastic Syndrome; Rasburicase; Elitek™

Summary:

      Primary Objectives:

      To determine the efficacy of rasburicase administered as a single dose followed by as needed
      dosing (investigational arm) as compared to fixed dosing for 5 days (standard treatment arm)
      in the treatment of patients at high risk or potential risk for tumor lysis syndrome.

      Secondary Objectives:

        1. To evaluate the plasma uric acid area under the curve (AUC) from baseline through 7 days

        2. To evaluate the incidence of renal insufficiency and electrolyte abnormalities.

        3. To determine the safety and immunogenicity of rasburicase.

        4. To evaluate the cost-effectiveness of the experimental treatment (investigational arm).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with hematological malignancies (leukemia/lymphoma) at high risk or potential
             risk for tumor lysis syndrome. High risk: hyperuricemia of malignancy (Uric acid
             levels >7.5); diagnosis of very aggressive lymphoma/leukemia based on Revised
             European-American Lymphoma (REAL) classification; acute myeloid leukemia, chronic
             myelocytic leukemia (CML) in blast crisis; high grade myelodysplastic syndrome only if
             they have >10% bone marrow blast involvement and given aggressive treatment similar to
             acute myeloid leukemia (AML) (continued on #2)

          2. (continued from # 1) Potential risk: diagnosis of aggressive lymphoma/leukemia based
             on (REAL) classification. Plus one or more of the following criteria: lactate
             dehydrogenase (LDH) >/= 2 x upper limit of normal (ULN); Stage III-IV disease; Stage
             I-II disease with at least 1 lymph node/tumor >5cm in diameter.

          3. ECOG performance status 0-3

          4. Life expectancy >3 months

          5. Negative pregnancy test (females of child bearing potential) within </=2 weeks of
             rasburicase dose and use of efficient contraceptive method (both males and females).
             Pregnancy test may be performed on serum (HCG) or urine (HCG)

          6. Signed written informed consent (approved by the Institutional Review Board/Ethics
             Committee) obtained prior to study entry

        Exclusion Criteria:

          1. Patient receiving any investigational drug for hyperuricemia within 30 days of planned
             first treatment with rasburicase

          2. Pregnancy or lactation

          3. Known history of significant allergy problem or documented history of asthma or
             asthmatic bronchitis

          4. Known history of glucose-6-phosphate dehydrogenase deficiency

          5. Known history of hemolysis and methemoglobinemia

          6. Previous therapy with urate oxidase

          7. Other conditions unsuitable for participation in the trial in the Investigator's
             opinion

          8. Unwillingness to comply with the requirements of the protocol

          9. Use of allopurinol within 72 hours of the study entry