Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

Efficacy and Safety of Two Comparable Single Low Doses of Rasburicase Followed by Allopurinol in Adult Patients With Malignancy

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I (1.5mg rasburicase); Patients receive 1.5mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6.	Drug: rasburicase; Given IV; Other Names: Elitek; NK-631; recombinant urate oxidase; Drug: allopurinol; Given PO; Other Names: Zyloprim; 4'-HPP; ALLO
EXPERIMENTAL: Arm II (3 mg rasburicase); Patients receive 3 mg of rasburicase IV over 30 minutes on day 1 and allopurinol PO QD on days 1-6.	Drug: rasburicase; Given IV; Other Names: Elitek; NK-631; recombinant urate oxidase; Drug: allopurinol; Given PO; Other Names: Zyloprim; 4'-HPP; ALLO

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Requiring Additional Doses of Rasburicase to Maintain a Uric Acid Level =< 7.5mg/dL	Count of partcicpants requiring additional doses of rasburicase to maintain a uric acid level =< 7.5mg/dL by treatment arm.	Up to day 7
Baseline White Blood Cell Count by Response	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).	Up to day 7
Area Under the Plasma Uric Acid Concentration-time Curve (AUC) From Baseline (Day 1) to Day 7	The mean area under the plasma uric acid concentration-time curve (AUC) from baseline (Day 1) to Day 7	Up to day 7
Safety of Low Single-doses of Rasburicase.	The number of patients with any adverse events .	up to day 7
Number of Patients Experiencing a Doubling of Serum Creatinine	Count of participants experiencing a doubling of serum creatinine	up to day 6

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 29, 2011
• Primary Completion (ACTUAL): May 28, 2015
• Study Completion (ACTUAL): May 28, 2016

Study Registration Dates

• First Submitted: March 2, 2012
• First Submitted That Met QC Criteria: March 23, 2012
• First Posted (ESTIMATE): March 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 9, 2018
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; DNA Virus Infections; Neoplastic Processes; Tumor Virus Infections; Precancerous Conditions; Epstein-Barr Virus Infections; Herpesviridae Infections; Lymphoma, B-Cell; Cell Transformation, Neoplastic; Carcinogenesis; Lymphoma; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence; Preleukemia; Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Rasburicase; Allopurinol
• Other Study ID Numbers: I 197711 (OTHER: Roswell Park Cancer Institute); P30CA016056 (U.S. NIH Grant/Contract); NCI-2011-03231 (REGISTRY: CTRP (Clinical Trial Reporting Program))