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

Alternate Title

3-AP and Cytarabine in Treating Patients With Hematologic Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	Pharmaceutical / Industry	VION-CLI-032 MDA-DM-030096, NCT00064090

Objectives

1. Determine the feasibility, tolerability, and toxic effects of 3-AP in combination with cytarabine in patients with hematologic malignancies.
2. Determine the maximum tolerated dose and phase II dose of cytarabine in this regimen in these patients.
3. Determine the biological effects of 3-AP and its interaction with cytarabine in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of 1 of the following hematologic malignancies:
  • Acute myeloid leukemia
  • Acute lymphoblastic leukemia
  • Chronic myelogenous leukemia (CML)
  • CML in blast crisis
  • Chronic lymphocytic leukemia
  • High-risk* myelodysplastic syndromes, including the following:
    • Refractory anemia with excess blasts (RAEB)
    • RAEB in transformation
    • Chronic myelomonocytic leukemia

   [Note: *High-risk myelodysplasia defined as having an International Performance Scoring System score of at least 1.5, based on adverse cytogenetics, greater than 10% blasts in marrow, and cytopenias in at least 2 lineages]




• Relapsed or refractory disease



• Ineligible for higher priority protocols

Prior/Concurrent Therapy:

Biologic therapy

• At least 1 week since prior growth factors, including the following:
  • Epoetin alfa
  • Filgrastim (G-CSF)
  • Sargramostim (GM-CSF)
  • Interleukin-3
  • Interleukin-11
• No concurrent anticancer immunotherapy

Chemotherapy

• At least 72 hours since prior hydroxyurea
• Recovered from prior chemotherapy
• No other concurrent anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

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

Surgery

• Not specified

Other

• At least 3 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressing disease)
• At least 1 week since prior nonmyelosuppressive therapy
• No other concurrent standard or investigational therapy for the malignancy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 2 months

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 2.0 mg/dL (unless considered due to malignancy)
• ALT or AST no greater than 3 times upper limit of normal
• Chronic hepatitis allowed

Renal

• Creatinine no greater than 2.0 mg/dL (unless considered due to malignancy)

Cardiovascular

• No myocardial infarction within the past 3 months
• No symptomatic coronary artery disease
• No arrhythmias (other than atrial fibrillation or flutter) requiring treatment
• No uncontrolled congestive heart failure

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Concurrent infections under active treatment with and controlled by antibiotics allowed
• No other concurrent life-threatening illness
• No mental deficit or psychiatric history that would preclude giving informed consent or complying with protocol

Expected Enrollment

Approximately 20-25 patients will be accrued for this study.

Outline

This is a pilot, dose-escalation study of cytarabine.

Patients receive 3-AP IV over 6 hours followed by cytarabine IV over 18 hours on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a response may receive an additional course as consolidation therapy.

Cohorts of 3-6 patients receive escalating doses of cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients receive treatment at that dose.

Trial Contact Information

Trial Lead Organizations

Vion Pharmaceuticals, Incorporated

Mario Sznol, MD, Protocol chair		Ph: 203-498-4210

Registry Information
Official Title		A Phase I Study of Triapine and Cytarabine in Patients with Hematologic Malignancies
Trial Start Date		2003-03-10
Trial Completion Date		2004-09-10
Registered in ClinicalTrials.gov		NCT00064090
Date Submitted to PDQ		2003-05-16
Information Last Verified		2008-08-22

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