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

Alternate Title

3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI UCCRC-12806B NCI-6283, NCT00077181, 6283

Objectives

Primary

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

Secondary

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

Entry 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

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

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

Expected Enrollment

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

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.

Odenike OM, Larson RA, Gajria D, et al.: Phase I study of the ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde-thiosemicarbazone (3-AP) in combination with high dose cytarabine in patients with advanced myeloid leukemia. Invest New Drugs 26 (3): 233-9, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Olatoyosi Odenike, MD, Principal investigator		Ph: 773-702-3354; 888-824-0200 Email: todenike@medicine.bsd.uchicago.edu

Registry Information
Official Title		A Phase I Study of Triapine in Combination with High Dose Ara-C (Hi-DAC) in Patients with Advanced Hematologic Malignancies
Trial Start Date		2003-12-10
Trial Completion Date		2008-07-09
Registered in ClinicalTrials.gov		NCT00077181
Date Submitted to PDQ		2003-12-11
Information Last Verified		2005-06-02
NCI Grant/Contract Number		CA69852, CA14599

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