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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

Phase 2
Open (Enrolling)

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Trial Information

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

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.

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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Barton A. Kamen, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Federal Government

Study ID:




Start Date:

July 1997

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • Leukemia



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