Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Aminopterin in Treating Patients With Refractory Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Any age	Pharmaceutical / Industry	ILEX-AMT-002/1997 UTSMC-AMT-002/1997, UTSMC-FDR001458, NCI-V99-1534, NCT00003305

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.

Entry Criteria

Disease Characteristics:

Histologically proven acute leukemia of any histologic type that is
refractory to known effective therapy

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

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

Expected Enrollment

This study will accrue a maximum of 25 patients per stratum, for a total of 75 
patients, within 3 years.

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.

Cole PD, Drachtman RA, Masterson M, et al.: Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia. Cancer Chemother Pharmacol 62 (1): 65-75, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Genzyme Oncology

Barton Kamen, MD, PhD, Protocol chair		Ph: 732-235-8864

Registry Information
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
Trial Start Date		1997-07-01
Registered in ClinicalTrials.gov		NCT00003305
Date Submitted to PDQ		1998-04-27
Information Last Verified		2008-08-08