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
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.
Interventional
Primary Purpose: Treatment
Barton A. Kamen, MD, PhD
Study Chair
Cancer Institute of New Jersey
United States: Federal Government
CDR0000066248
NCT00003305
July 1997
Name | Location |
---|---|
University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
Medical City Dallas Hospital | Dallas, Texas 75230 |
Herbert Irving Comprehensive Cancer Center | New York, New York 10032 |
Cancer Institute of New Jersey | New Brunswick, New Jersey 08901 |
Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
Advanced Urology Medical Center | Anaheim, California 92801 |
South Coast Urological Medical Group | Laguana Hills, California 92653 |
Urology Specialists, P.C. | Waterbury, Connecticut 06708 |
Barzell, Whitmore, Treiman and Dunne - The Urology Treatment Center | Sarasota, Florida 34239 |
206 Research Associates | Greenbelt, Maryland 20770 |
Mid Atlantic Clinical Research | Rockville, Maryland 20850 |
Medical & Clinical Research Associates, LLC | Bay Shore, New York 11706 |
Urology Centers of North Texas | Dallas, Texas 75231 |
Urology San Antonio Research | San Antonio, Texas 78229 |