Aminopterin in Treating Patients With Refractory Leukemia

NCT ID: NCT00003305

Last Updated: 2014-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-07-31

Study Completion Date

2007-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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aminopterin

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role lead

Principal Investigators

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Barton A. Kamen, MD, PhD

Role: STUDY_CHAIR

Rutgers Cancer Institute of New Jersey

Locations

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Advanced Urology Medical Center

Anaheim, California, United States

Site Status

South Coast Urological Medical Group

Laguana Hills, California, United States

Site Status

Urology Specialists, P.C.

Waterbury, Connecticut, United States

Site Status

Barzell, Whitmore, Treiman and Dunne - The Urology Treatment Center

Sarasota, Florida, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

206 Research Associates

Greenbelt, Maryland, United States

Site Status

Mid Atlantic Clinical Research

Rockville, Maryland, United States

Site Status

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Medical & Clinical Research Associates, LLC

Bay Shore, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

Urology Centers of North Texas

Dallas, Texas, United States

Site Status

Urology San Antonio Research

San Antonio, Texas, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Cole PD, Drachtman RA, Masterson M, Smith AK, Glod J, Zebala JA, Lisi S, Drapala DA, Kamen BA. Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2008 Jun;62(1):65-75. doi: 10.1007/s00280-007-0576-7. Epub 2007 Sep 2.

Reference Type RESULT
PMID: 17768625 (View on PubMed)

Other Identifiers

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ILEX-AMT-002/1997

Identifier Type: -

Identifier Source: secondary_id

UTSMC-AMT-002/1997

Identifier Type: -

Identifier Source: secondary_id

UTSMC-FDR001458

Identifier Type: -

Identifier Source: secondary_id

NCI-V99-1534

Identifier Type: -

Identifier Source: secondary_id

CDR0000066248

Identifier Type: -

Identifier Source: org_study_id

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