Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

Phase 2

Terminated

Conditions: Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Blastic Phase Chronic Myelogenous Leukemia
Contiguous Stage II Adult Burkitt Lymphoma
de Novo Myelodysplastic Syndromes
Recurrent Adult Burkitt Lymphoma
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Adult Acute Myeloid Leukemia
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Previously Treated Myelodysplastic Syndromes
Stage III Adult Burkitt Lymphoma

Brief Summary: This randomized phase II trial studies how well giving rasburicase together with allopurinol works in treating patients with hematologic malignancies. Rasburicase may reduce the level of uric acid in the blood. Allopurinol may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known which dose of rasburicase is more effective in treating hematologic malignancies when given together with or without allopurinol.

Detailed Description: PRIMARY OBJECTIVES:

I. To prospectively evaluate the efficacy, as defined by uric acid response rate, of 2 different single low doses of rasburicase followed by allopurinol in 2 treatment arms.

SECONDARY OBJECTIVES:

I. To estimate the proportion of patients requiring additional doses of rasburicase to maintain a uric acid level =\< 7.5mg/dL on day 2 through day 6.

II. To identify differential characteristics of the patients who do not respond to treatment.

III. To measure the area under the plasma uric acid concentration-time curve (AUC) from baseline (day 1) to day 7, time to plasma uric acid level less than or equal to 7.5mg/dL.

IV. To evaluate the rate of patients requiring hemodialysis (HD) V. To evaluate the safety of low single-doses of rasburicase. VI. To evaluate the rate of patients expressing a doubling of serum creatinine.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive 1.5mg of rasburicase intravenously (IV) over 30 minutes on day 1\* and allopurinol orally (PO) once daily (QD) on days 1-6.

ARM II: Patients receive 3 mg of rasburicase IV over 30 minutes on day 1\* and allopurinol PO QD on days 1-6.

NOTE: \*Patients with serum uric acid \>= 7.5mg/dl also receive rasburicase IV on days 2-3.

After completion of study treatment, patients are followed up at 30 days.

Recruitment & Eligibility

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) status of 0-3
Active leukemia and Burkitt leukemia/lymphoma treated in-house that puts them at risk for tumor lysis syndrome (TLS)
Serum uric acid level >= 7.5mg/dL and high risk for TLS as defined by:
- A diagnosis of acute myeloid leukemia (AML), or
- A diagnosis of blast-phase chronic myeloid leukemia (CML), or
- A diagnosis of high-grade myelodysplastic syndrome (MDS) with >= 10% blast bone marrow blast involvement, or
- Acute lymphoblastic leukemia (ALL), or
- Burkitt leukemia/lymphoma
Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

History of asthma
History of severe or life threatening atopic allergy
Hypersensitivity to uricases
Known prior sensitivity to allopurinol
Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
Recent prior history of uricolytic therapy defined as therapy within the last 7 days

Arm && Interventions

Group	Intervention	Description
Arm II (3 mg rasburicase)	rasburicase	Patients receive 3 mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6.
Arm I (1.5mg rasburicase)	rasburicase	Patients receive 1.5mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6.
Arm I (1.5mg rasburicase)	allopurinol	Patients receive 1.5mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6.
Arm II (3 mg rasburicase)	allopurinol	Patients receive 3 mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6.

Primary Outcome Measures

Name	Time	Method
Probability of Obtaining a Uric Acid Level =< 7.5mg/dL	Within 24 hours of rasburicase treatment	The proportion of patients able to achieve and/or maintain a uric acid level =\< 7.5mg/dL for each treatment arm.

Secondary Outcome Measures

Name	Time	Method
Baseline White Blood Cell Count by Response	Up to day 7	The mean baseline white blood cell count of patients with a complete response (CR) (patients who achieved uric acid level =\< 7.5mg/dL) and no CR (patients with uric acid level \> 7.5mg/dL).
Number of Patients Requiring Additional Doses of Rasburicase to Maintain a Uric Acid Level =< 7.5mg/dL	Up to day 7	Count of partcicpants requiring additional doses of rasburicase to maintain a uric acid level =\< 7.5mg/dL by treatment arm.
Area Under the Plasma Uric Acid Concentration-time Curve (AUC) From Baseline (Day 1) to Day 7	Up to day 7	The mean area under the plasma uric acid concentration-time curve (AUC) from baseline (Day 1) to Day 7
Safety of Low Single-doses of Rasburicase.	up to day 7	The number of patients with any adverse events .
Number of Patients Experiencing a Doubling of Serum Creatinine	up to day 6	Count of participants experiencing a doubling of serum creatinine