Aminopterin in Treating Patients With Refractory Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00003305
Recruitment Status : Completed
First Posted : August 2, 2004
Last Update Posted : January 6, 2014
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Leukemia Drug: aminopterin Drug: leucovorin calcium Phase 2

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  (Clinical Trial)
Estimated Enrollment : 75 participants
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 1997
Actual Study Completion Date : September 2007

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00003305

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

Publications of Results: Identifier: NCT00003305     History of Changes
Other Study ID Numbers: CDR0000066248
First Posted: August 2, 2004    Key Record Dates
Last Update Posted: January 6, 2014
Last Verified: August 2008

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Protective Agents
Physiological Effects of Drugs
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action