Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

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.

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