Pharmacokinetic Evaluation of Rasburicase in Patients With Leukemia and/or Lymphoma at High Risk of TLS

July 31, 2012 updated by: M.D. Anderson Cancer Center

Pharmacokinetic Evaluation of Rasburicase Dosed for 5 Consecutive Days as Uricolytic Therapy in Adult Patients With Leukemia and/or Lymphoma at High or Potential Risk of Tumor Lysis Syndrome (TLS)

Primary

1. To determine the pharmacokinetic (PK) parameters of rasburicase in adult patients with leukemia and/or lymphoma at high risk or potential risk of tumor lysis syndrome (TLS)

Secondary

  1. To evaluate plasma uric acid AUC from baseline (within 4 hours prior to first rasburicase treatment) through 48 hours after the last per-protocol planned administration of rasburicase treatment;
  2. To evaluate the safety of rasburicase in adult patients with leukemia and/or lymphoma.
  3. To evaluate incidence, duration, and type of immune responses (IgG, IgE, and neutralizing antibody) to rasburicase.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the start of chemotherapy. A high level of uric acid may lead to reduced kidney function or kidney failure.

TLS occurs when high uric acid levels are caused by breakdown of tumor cells after the start of chemotherapy. The dead tumor cells can release uric acid and other symptoms of kidney failure, such as excessive amounts of potassium and phosphorus, into the blood.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. Your complete medical history will be recorded, and you will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. You will have blood drawn (about 2 tablespoons) for routine tests. Women who are able to have children must have a negative blood (a sample will be used from the routine blood draw) or urine pregnancy test.

If you are found to be eligible to take part in this study, you will receive rasburicase by a needle in your vein over 30 minutes once a day for 5 days in a row. You will receive chemotherapy within 4-24 hours after your first dose of rasburicase.

On Days 1-5 (study drug treatment period), you will have a physical exam, including measurement of your vital signs. During this time, you will have blood drawn (about 2 tablespoons each) once a day for routine tests.

You will have blood drawn (less than 1 teaspoon each) for PK testing at different time points throughout this study. PK tests measure the level of the study drug in the blood at different times. You will have a total of 14 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then at 30 minutes and at 4, 8, 24, 48, 72, 96, 96.5,100,104,120 (Day 6),168 (Day 8), and 336 (Day 15) hours after your dose of the study drug.

You will have blood drawn (less than 1 teaspoon each) to measure the level of uric acid in your blood at different time points throughout this study so that researchers can learn the effectiveness of the study drug on your disease. You will have a total of 7 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then at 4, 24, 48, 72, 96,120 (Day 6), and 144 (Day 7) hours after your dose of the study drug.

You will also have blood drawn (less than 1 teaspoon each) for antibody testing at different time points throughout this study. Antibody testing is a method to check for proteins (IgG) made by your body that show that your body is reacting to rasburicase. You will have at least 5 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then on Day 14, Day 35, and at 3 and 6 months after your dose of the study drug.

If you have a positive IgG (antibody protein) at the 6-month blood draw for antibody testing, you will continue to have blood drawn (less than 1 teaspoon) every 6 months until your antibody protein is negative.

If you experience any side effects related to allergic reactions during treatment with the study drug (up to 30 days after your last dose of the study drug), you will have an additional blood draw (less than 1 teaspoon) for antibody testing within 48 hours after having the reaction.

You will be taken off this study if your disease gets worse or you experience any intolerable side effects.

You will have assessments after the end of your study drug treatment (from Days 1 to 5). These assessments will include a physical exam, including measurement of your vital signs, on Days 14 and 35. You will also have blood drawn (about 2 tablespoons each) for routine tests on Days 8 and 14.

This is an investigational study. Rasburicase is authorized by the FDA for use (in adults) in research only. Rasburicase will be provided free of charge during this study. Up to 20 patients will take part in this multicenter study. Up to 20 can be enrolled at M. D. Anderson.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Age >/= 18
  2. Risk of TLS: A. High risk: hyperuricemia of malignancy; diagnosis of aggressive lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification; acute myeloid leukemia in blast crisis; high grade myelodysplastic syndrome only if they have >10% bone marrow blast involvement and given aggressive treatment similar to AML; OR B. Potential risk: diagnosis of aggressive lymphoma/leukemia based on (REAL) classification. Plus one or more of the following criteria: LDH >/=2 x ULN; Stage III-IV disease; Stage I-II disease with at least 1 lymph node/tumor >5cm in diameter.
  3. ECOG performance status 0-3
  4. Life expectancy >3 months
  5. Negative pregnancy test (females of child bearing potential) within </=2 weeks of rasburicase dose and use of efficient contraceptive method (both males and females). Pregnancy test may be performed on serum (HCG) or urine (HCG)
  6. Signed written informed consent (approved by the Institutional Review Board/Ethics Committee) obtained prior to study entry

Exclusion Criteria:

  1. Patient receiving any investigational drug for hyperuricemia within 30 days of planned first treatment with rasburicase
  2. Pregnancy or lactation
  3. Known history of significant allergy problem or documented history of asthma or asthmatic bronchitis
  4. Known history of glucose-6-phosphate dehydrogenase deficiency
  5. Known history of hemolysis and methemoglobinemia
  6. Positive tests for HBs antigen, HCV antibodies, or HIV-1, 2 antibodies
  7. Hypersensitivity to uricases or any of the excipients
  8. Previous therapy with urate oxidase
  9. Other conditions unsuitable for participation in the trial in the Investigator's opinion
  10. Unwilling to comply with the requirements of the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rasburicase
Drug: Rasburicase
0.15mg/kg intravenously over 30 minutes once per day for 5 consecutive days.
Other Names:
  • Elitek

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Effectiveness of rasburicase in treatment of patients with leukemia and/or lymphoma who are at high or potential risk for TLS.
Time Frame: 4 Years
4 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Sanofi

Investigators

  • Principal Investigator: Saroj Vadhan-Raj, M.D., M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

April 1, 2007

Study Completion (Actual)

April 1, 2007

Study Registration Dates

First Submitted

August 2, 2006

First Submitted That Met QC Criteria

August 2, 2006

First Posted (Estimate)

August 4, 2006

Study Record Updates

Last Update Posted (Estimate)

August 1, 2012

Last Update Submitted That Met QC Criteria

July 31, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006-0298

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on Rasburicase

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Canada

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe