Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

Roswell Park Comprehensive Cancer Center

Status and phase: Terminated; Phase 2

Conditions: Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Untreated Adult Acute Lymphoblastic Leukemia; Stage I Adult Burkitt Lymphoma; Stage III Adult Burkitt Lymphoma; Previously Treated Myelodysplastic Syndromes; Contiguous Stage II Adult Burkitt Lymphoma; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Recurrent Adult Burkitt Lymphoma; Stage IV Adult Burkitt Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Noncontiguous Stage II Adult Burkitt Lymphoma; Adult Acute Myeloid Leukemia With Del(5q)

Treatments: Drug: rasburicase; Drug: allopurinol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01564277

P30CA016056 (U.S. NIH Grant/Contract)

I 197711 (Other Identifier)

NCI-2011-03231 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Arm I (1.5mg rasburicase)

Experimental group

Description:

Patients receive 1.5mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6.

Treatment:

Drug: allopurinol

Drug: rasburicase

Arm II (3 mg rasburicase)

Experimental group

Description:

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

Treatment:

Drug: allopurinol

Drug: rasburicase