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Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

This study has been terminated.
(low accrual)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01564277
First received: March 2, 2012
Last updated: May 28, 2015
Last verified: May 2015
  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: Up to day 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: Up to day 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.

  • Rate of patients able to maintain a uric acid level =< 7.5mg/dL [ Time Frame: Up to day 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.

  • Differential characteristics of patients unable to achieve and/or maintain a uric acid level =< 7.5mg/dL [ Time Frame: Up to day 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.


Enrollment: 21
Study Start Date: September 2011
Primary Completion Date: May 2015 (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: rasburicase
Given IV
Other Names:
  • Elitek
  • NK-631
  • recombinant urate oxidase
Drug: allopurinol
Given PO
Other Names:
  • 4'-HPP
  • ALLO
  • Zyloprim

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Eunice Wang, MD Roswell Park Cancer Institute
  More Information

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01564277     History of Changes
Other Study ID Numbers: I 197711  NCI-2011-03231  I 197711  P30CA016056 
Study First Received: March 2, 2012
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Leukemia
Syndrome
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Burkitt Lymphoma
Blast Crisis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myeloproliferative Disorders
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell

ClinicalTrials.gov processed this record on December 02, 2016