Clinical trial NCT00003305: Aminopterin in Treating Patients With Refractory Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-08-02
Enrollment: 75
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Urology Medical Center
state: California
city: Laguana Hills
country: United States
facility: South Coast Urological Medical Group
state: California
city: Waterbury
country: United States
facility: Urology Specialists, P.C.
state: Connecticut
city: Sarasota
country: United States
facility: Barzell, Whitmore, Treiman and Dunne - The Urology Treatment Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Greenbelt
country: United States
facility: 206 Research Associates
state: Maryland
city: Rockville
country: United States
facility: Mid Atlantic Clinical Research
state: Maryland
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Bay Shore
country: United States
facility: Medical & Clinical Research Associates, LLC
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: Urology Centers of North Texas
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Barton A. Kamen, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.