RATIONALE: Drugs used in chemotherapy, such as cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may help cytarabine kill more cancer cells by making them more sensitive to the drug.

PURPOSE: Phase I trial to study the effectiveness of combining 3-AP with high-dose cytarabine in treating patients who have advanced hematologic malignancies.

Condition	Treatment or Intervention	Phase
adult acute lymphoblastic leukemia adult acute myeloid leukemia Chronic Myelogenous Leukemia secondary acute myeloid leukemia	Drug: 3-AP  Drug: cytarabine  Procedure: chemotherapy  Procedure: high-dose chemotherapy	Phase I

OBJECTIVES: Primary

• Determine the maximum tolerated dose of 3-AP (Triapine®) administered with high-dose cytarabine in patients with advanced hematologic malignancies.

Secondary

• Determine the clinical activity of this regimen in these patients.
• Determine the effect of treatment with 3-AP (Triapine®) on intracellular levels of cytarabine in these patients.

OUTLINE: This is a dose-escalation study of 3-AP (Triapine®).

Patients receive high-dose cytarabine IV over 2 hours on days 1-5 and 3-AP (Triapine®) IV over 2 hours on days 2-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients in each stratum receive escalating doses of 3-AP (Triapine®) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for up to 2 years.

PROJECTED ACCRUAL: A total of 6-48 patients (3-24 per stratum) will be accrued for this study within 15-24 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following hematologic malignancies:
• Relapsed or refractory acute myeloid leukemia (AML)
• Relapsed or refractory acute lymphoblastic leukemia
• Secondary AML, including AML arising from antecedent hematologic diseases, such as myelodysplastic syndromes or myeloproliferative disorders OR therapy-related AML
• Chronic myeloid leukemia in accelerated or blast phase
• Refractory to standard therapy or no standard therapy exists
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• CALGB 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• No G6PD deficiency

Hepatic

• Bilirubin < 2.0 mg/dL (unless due to Gilbert’s syndrome)
• AST and ALT < 2.5 times upper limit of normal (ULN)

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Pulmonary

• No pulmonary disease requiring oxygen

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to study drugs
• No neuropathy
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent biologic agents

Chemotherapy

• At least 72 hours since prior hydroxyurea
• At least 2 weeks since other prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from all prior therapy
• At least 4 weeks since prior investigational agents
• No other concurrent investigational therapy
• No other concurrent anticancer therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States; Recruiting

Study chairs or principal investigators

Olatoyosi M. Odenike, MD,  Principal Investigator,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000349659; UCCRC-12806B; NCI-6283
Record last reviewed:  May 2004
Record first received:  February 10, 2004
ClinicalTrials.gov Identifier:  NCT00077181
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-22