3-AP and Cytarabine in Treating Patients With Hematologic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as cytarabine use different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth and 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 cytarabine with 3-AP in treating patients who have relapsed or refractory hematologic cancer.

Detailed Description
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OBJECTIVES: Determine the feasibility, tolerability, and toxic effects of 3-AP in combination with cytarabine in patients with hematologic malignancies. Determine the maximum tolerated dose and phase II dose of cytarabine in this regimen in these patients. Determine the biological effects of 3-AP and its interaction with cytarabine in these patients. 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. PROJECTED ACCRUAL: Approximately 20-25 patients will be accrued for this study.

Official Title
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A Phase I Study of Triapine and Cytarabine in Patients With Hematologic Malignancies

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Drug: cytarabine
* Drug: triapine


Participation Criteria
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Eligibility Criteria
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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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cytarabine|nan|
|Drug: triapine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, blastic phase chronic myelogenous leukemia, refractory chronic lymphocytic leukemia, relapsing chronic myelogenous leukemia, chronic myelomonocytic leukemia, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)