Aminopterin in Treating Patients With Refractory Leukemia

Sponsor

Genzyme, a Sanofi Company (Industry)

Overall Status

Completed

CT.gov ID

NCT00003305

Collaborator

(none)

Enrollment

Locations

122

Duration (Months)

5.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated 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 :

Jul 1, 1997

Actual Study Completion Date :

Sep 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Urology Medical Center	Anaheim	California	United States	92801
2	South Coast Urological Medical Group	Laguana Hills	California	United States	92653
3	Urology Specialists, P.C.	Waterbury	Connecticut	United States	06708
4	Barzell, Whitmore, Treiman and Dunne - The Urology Treatment Center	Sarasota	Florida	United States	34239
5	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
6	206 Research Associates	Greenbelt	Maryland	United States	20770
7	Mid Atlantic Clinical Research	Rockville	Maryland	United States	20850
8	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
9	Medical & Clinical Research Associates, LLC	Bay Shore	New York	United States	11706
10	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
11	Medical City Dallas Hospital	Dallas	Texas	United States	75230
12	Urology Centers of North Texas	Dallas	Texas	United States	75231
13	Urology San Antonio Research	San Antonio	Texas	United States	78229
14	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105