Aminopterin in Treating Patients With Refractory Leukemia

January 3, 2014 updated by: Genzyme, a Sanofi Company

A Phase II Trial of Aminopterin in Adults and Children With Refractory Acute Leukemia Grant Application Title: A Phase II Trial of Aminopterin in Acute Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of aminopterin in treating patients who have refractory leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Determine the maximum tolerated dose of aminopterin in patients with refractory leukemia and minimal previous exposure to antifolate agents. II. Determine the antileukemic activity of aminopterin in adults and children with acute myelogenous and acute lymphoblastic leukemia for whom conventional therapy has failed. III. Confirm that aminopterin can be administered for four consecutive weeks when followed with minimal leucovorin calcium rescue and determine the minimal amount of leucovorin calcium required for each patient. IV. Confirm bioavailability data on oral aminopterin by performing limited sampling pharmacokinetics. V. Correlate blast uptake of aminopterin in vitro with clinical response.

OUTLINE: This is an open label study. Patients are stratified according to age and type of leukemia: Stratum I: Under 20 years old with acute lymphoblastic leukemia (ALL) in second or greater relapse Stratum II: Greater than 20 years old with ALL in first or greater relapse Stratum III: Patients of any age with acute myelogenous leukemia (AML) in first or greater relapse Patients receive aminopterin every 12 hours for 2 doses weekly for 4 weeks. Aminopterin is administered intravenously over 20 minutes for the first, second, and fourth doses, and orally for the third dose. The fifth and all subsequent doses are administered orally if bioavailability is acceptable. Patients receive oral leucovorin calcium every 12 hours for 2 doses beginning 24 hours after the last dose of aminopterin each week. If toxicity is limited for 2 consecutive weeks, the dose of leucovorin calcium is decreased to 1 dose administered 24 hours after the last dose of aminopterin each week. If this schedule is tolerated for 2 consecutive weeks, then leucovorin calcium is discontinued. Patients continue therapy for up to 15 months in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months.

PROJECTED ACCRUAL: This study will accrue a maximum of 25 patients per stratum, for a total of 75 patients, within 3 years.

Study Type

Interventional

Enrollment (Anticipated)

75

Phase

  • Phase 2

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
    • California
      • Anaheim, California, United States, 92801
        • Advanced Urology Medical Center
      • Laguana Hills, California, United States, 92653
        • South Coast Urological Medical Group
    • Connecticut
      • Waterbury, Connecticut, United States, 06708
        • Urology Specialists, P.C.
    • Florida
      • Sarasota, Florida, United States, 34239
        • Barzell, Whitmore, Treiman and Dunne - The Urology Treatment Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Cancer Research Center
    • Maryland
      • Greenbelt, Maryland, United States, 20770
        • 206 Research Associates
      • Rockville, Maryland, United States, 20850
        • Mid Atlantic Clinical Research
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute Of New Jersey
    • New York
      • Bay Shore, New York, United States, 11706
        • Medical & Clinical Research Associates, LLC
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center
    • Texas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • Dallas, Texas, United States, 75231
        • Urology Centers of North Texas
      • San Antonio, Texas, United States, 78229
        • Urology San Antonio Research
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Histologically proven acute leukemia of any histologic type that is refractory to known effective therapy

PATIENT CHARACTERISTICS: Age: Any age Performance status: Karnofsky 50-100% Life expectancy: At least 6 weeks Hematopoietic: Not specified Hepatic: Bilirubin no greater than 1.5 mg/dL ALT no greater than 5 times upper limit of normal Renal: Creatinine normal for age Cardiovascular: No unstable angina No uncontrolled arrhythmia Pulmonary: No third space effusion Other: No severe uncontrolled infection Adequate nutritional status At least third percentile for weight Normal total serum protein Normal albumin/globulin ratio No serious concurrent physical or mental illness Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 months since prior bone marrow transplantation Recovered from prior biologic therapy No concurrent anticancer biologic therapy Chemotherapy: Recovered from prior chemotherapy No concurrent anticancer chemotherapy Endocrine therapy: Recovered from prior endocrine therapy No concurrent anticancer endocrine therapy No concurrent dexamethasone or other steroids as antiemetic agents Radiotherapy: No concurrent anticancer radiotherapy Surgery: Not specified Other: No concurrent dairy products for 2-4 hours before, during, or 2-4 hours after study drug No concurrent trimethoprim-sulfamethoxazole or dapsone as prophylaxis for Pneumocystis infection No concurrent multivitamins containing folic acid

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

Collaborators and Investigators

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

Sponsor

Genzyme, a Sanofi Company

Investigators

  • Study Chair: Barton A. Kamen, MD, PhD, Rutgers Cancer Institute of New Jersey

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.

General Publications

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, 1997

Study Completion (Actual)

September 1, 2007

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 30, 2004

First Posted (Estimate)

August 2, 2004

Study Record Updates

Last Update Posted (Estimate)

January 6, 2014

Last Update Submitted That Met QC Criteria

January 3, 2014

Last Verified

August 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000066248
  • ILEX-AMT-002/1997
  • UTSMC-AMT-002/1997
  • UTSMC-FDR001458
  • NCI-V99-1534

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.

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