Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

This study is currently recruiting participants.
Verified March 2014 by Roswell Park Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01564277
First received: March 2, 2012
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
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(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
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
Noncontiguous Stage II Adult Burkitt Lymphoma
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Stage I Adult Burkitt Lymphoma
Stage III Adult Burkitt Lymphoma
Stage IV Adult Burkitt Lymphoma
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: rasburicase
Drug: allopurinol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Two Comparable Single Low Doses of Rasburicase Followed by Allopurinol in Adult Patients With Malignancy

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Probability of obtaining a uric acid level =< 7.5mg/dL [ Time Frame: Within 24 hours of rasburicase treatment ] [ Designated as safety issue: No ]
    The sample proportion responding and the lower one-sided Wilson Score confidence limits will be calculated for each treatment arm. Other descriptive statistics and graphical comparisons will be provided as needed.


Secondary Outcome Measures:
  • Rate of patients that maintain a uric acid level =< 7.5mg/dL [ Time Frame: Days 2-6 following a single dose of rasburicase ] [ Designated as safety issue: No ]
    The sample proportion responding and the lower one-sided Wilson Score confidence limits will be calculated for each treatment arm. Other descriptive statistics and graphical comparisons will be provided as needed.

  • Rate of patients requiring additional doses of rasburicase to maintain a uric acid level =< 7.5mg/dL [ Time Frame: Days 2-6 ] [ Designated as safety issue: No ]
    The sample proportion responding and the lower one-sided Wilson Score confidence limits will be calculated for each treatment arm. Other descriptive statistics and graphical comparisons will be provided as needed.

  • Comparison of rate of patients able to maintain a uric acid level =< 7.5mg/dL between the two treatment arms [ Time Frame: Days 2-6 ] [ Designated as safety issue: No ]
    The sample proportion responding and the lower one-sided Wilson Score confidence limits will be calculated for each treatment arm. Other descriptive statistics and graphical comparisons will be provided as needed.

  • Identification and comparison of differential characteristics of patients unable to achieve and/or maintain a uric acid level =< 7.5mg/dL [ Time Frame: Days 2-6 ] [ Designated as safety issue: No ]
    The sample proportion responding and the lower one-sided Wilson Score confidence limits will be calculated for each treatment arm. Other descriptive statistics and graphical comparisons will be provided as needed.


Estimated Enrollment: 36
Study Start Date: September 2011
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • 4'-HPP
  • ALLO
  • Zyloprim
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: allopurinol
Given PO
Other Names:
  • 4'-HPP
  • ALLO
  • Zyloprim
Drug: rasburicase
Given IV
Other Names:
  • Elitek
  • NK-631
  • recombinant urate oxidase

Detailed Description:

PRIMARY OBJECTIVES:

I. To prospectively evaluate the efficacy, as defined by uric acid response rate, of 2 different 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01564277

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    AskRPCI@roswellpark.org   
Principal Investigator: Meir Wetzler         
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Meir Wetzler Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01564277     History of Changes
Other Study ID Numbers: I 197711, NCI-2011-03231
Study First Received: March 2, 2012
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Blast Crisis
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Cell Transformation, Neoplastic
Neoplastic Processes
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Pathologic Processes
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on April 17, 2014