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Uric Acid

Allopurinol

Rasburicase

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Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1 (21 day cycle).

Participants randomized to Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.

Participants randomized to Allopurinol (300 mg/day) by vein each day on Days 1-5 of Cycle 2.

Cycle 1: 3 mg/kg by vein on Day 1, plus as needed dosing (until day 5), during Cycle 1.

Cycle 2 Arm A: 0.15 mg/kg by vein on Day 1 of Cycle 2, plus as needed dosing (until day 5), during Cycle 2.

Arm B: 300 mg/day by vein, as standard of care, over 30 minutes each day on days 1-5 of cycle 2 in 21 day cycle.

Saroj Vadhan-Raj, MD

The goal of this clinical research study is to learn if using Elitek (rasburicase) for 2 cycles can help to control or prevent TLS better than 1 cycle of rasburicase and 1 cycle of allopurinol. The safety of this treatment will also be studied.

Study Drugs:

Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the beginning of chemotherapy. A high level of uric acid results from TLS and can lead to kidney failure.

Allopurinol is designed to help block uric acid. It is the standard of care for helping to control increased uric acid levels caused by TLS.

Study Groups and Drug Administration:

Each cycle will last about 3 weeks.

If you are found to be eligible to take part in this study, you will receive rasburicase by vein over about 30 minutes on Day 1 of Cycle 1 (about 4 hours before you begin receiving chemotherapy). If the doctor thinks it is needed, you may also receive the drug on Days 2-5 of Cycle 1.

For Cycle 2, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. There is an equal chance of being assigned to either group:

* If you are in Group A, you will receive rasburicase on Day 1 of Cycle 2. If the doctor thinks it is needed, you may also receive the drug on Days 2-5 of Cycle 2.
* If you are in Group B, you will receive allopurinol by vein over 30 minutes each day on Days 1-5 of Cycle 2.

Group B Participants: If your uric acid blood levels continue to increase in Cycle 2 and you show symptoms of tumor lysis syndrome, you may receive rasburicase as a single dose. If the doctor thinks it is needed, you may also receive 1 or more additional dose(s).

Study Visits:

On Day 1 of Cycle 1:

* Blood (about 1 teaspoon) will be drawn to check uric acid levels before and 4 hours after you receive rasburicase.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* Blood (about 1 teaspoon) will be drawn for antibody testing. Antibodies are proteins made by the body that the immune system uses to help prevent disease.

On Days 2-5 of Cycle 1:

* Blood (about 1 teaspoon) will be drawn to check uric acid levels.
* Blood (about 2 tablespoon) will be drawn for routine tests.

At the end of both cycles, blood (about 1 teaspoon) will be drawn for antibody testing.

Length of Study:

You will receive drugs on this study for up to 2 cycles. You will be taken off study if intolerable side effects occur.

Your participation in the study will be over after the follow-up visit.

Follow-Up:

Three (3) months after the end of Cycle 2, blood (about 1 teaspoon) will be drawn for antibody testing.

This is an investigational study. Allopurinol is commercially available and FDA approved to treat TLS. Rasburicase is commercially available and FDA approved for treating TLS for 1 cycle in patients with leukemia, lymphoma, and solid tumor cancers who are receiving anti-cancer therapy. It is investigational to give rasburicase for 2 cycles.

Up to 55 patients will take part in this study. All will be enrolled at MD Anderson.

Rasburicase in Patients at High Risk for Tumor Lysis Syndrome (TLS) During Cycle-2

A Randomized Phase 2 Study to Evaluate the Efficacy of Rasburicase in Patients at Risk for TLS During Two Cycles of Chemotherapy

Number of participants (incidence) of LTLS in the two arms, as defined by the Cairo-Bishop criteria , during cycle 2.

Cairo-Bishop criteria:

Uric acid x ≥ 476 μmol/l or 25% increase from baseline Potassium x ≥ 6·0 mmol/l or 25% increase from baseline Phosphorous x ≥ 2·1 mmol/l (children), x ≥1·45 mmol/l (adults) or 25% increase from baseline Calcium x ≤ 1·75 mmol/l or 25% decrease from baseline Laboratory tumour lysis syndrome (LTLS) is defined as either a 25% change or level above or below normal, as defined above, for any two or more serum values of uric acid, potassium, phosphate, and calcium within 3d before or 7d after the initiation of chemotherapy.

Number of participants with normalized UAL as determined by a uric acid blood test at either 24 hours. A uric acid blood test, also known as a serum uric acid measurement, determines how much uric acid is present in the blood where normal levels are 2.4-6.0 mg/dL (female) and 3.4-7.0 mg/dL (male).

Sanofi

M.D. Anderson Cancer Center

Cycle 1: Rasburicase Alone

Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.

Cycle 2: Arm A (Rasburicase)

Allopurinol (300 mg/day) each day on Days 1-5 of Cycle 2.

Cycle 2: Arm B (Allopurinol)

Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1

Rasburicase Alone

Age, Continuous

Cycle 2, Arm A

Cycle 2, Arm B

Baseline age of participants randomized in Cycle 2.

Each row represents continuous age for each randomized arm in Cycle 2, Arm A Rasburicase (N=21) and Arm B Allopurinol (N=25), total 46.

Age, Customized

Cycle 1, Rasburicase

Measure rows divide Cycle 1 (55) then those randomized to Cycle 2 Arm A (21) and Arm B (25).

Sex: Female, Male

United States

Region of Enrollment

>/=2

Participant performance status (PS) using the ECOG scale which ranges from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden.

Eastern Cooperative Oncology Group (ECOG) PS, Cycle 1

Arm A

Arm B

Row represents PS as defined above for each randomized arm in Cycle 2, Arm A (21) and Arm B (25), total 46.

Randomized arms in Cycle 2 Arm A (21) and Arm B (25).

ECOG PS, Cycle 2

High risk: Hyperuricemia of malignancy (Uric acid level\>7.5); or diagnosis aggressive lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification; acute myeloid leukemia, CML in blast crisis; high grade myelodysplastic syndrome only if \>10% bone marrow blast involvement, aggressive treatment similar to acute myeloid leukemia (AML). Potential risk: Diagnosis aggressive lymphoma/leukemia (REAL classification) + 1/\> criteria: lactate dehydrogenase (LDH) \>2 x upper limit of normal (UNL); Stage III-IV disease; Stage I-II disease + 1/\> lymph node/tumor \>5 cm diameter.

Tumor Lysis Syndrome (TLS) Risk

Randomized Cycle 2 Arm A (21) and Arm B (25).

Baseline Plasma Uric Acid (PUA)

Of 55 enrolled on study, 52 participants were treated in Cycle 1 Rasburicase alone, only 46 randomized to Cycle 2 Arm A Rasburicase (21) and Arm B Allopurinol (25).

Saroj Vadhan, MD/Professor, Cytokine & Supportive Oncology

Arm A (Rasburicase)

Arm B (Allopurinol)

All 46 participants treated in randomized cycle 2 of study were included in analysis.

Number of Participants (Incidence) of LTLS (Laboratory Tumor Lysis Syndrome)

One participant in Arm A missed one UA level assessment.

Spots Global Cancer Trial Database for recombinant urate oxidase