Brief Title
3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies
Official Title
A Phase I Study of Triapine in Combination With High Dose Ara-C (Hi-DAC) in Patients With Advanced Hematologic Malignancies
Brief Summary
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. This phase I trial is studying the side effects and best dose of 3-AP when given with high-dose cytarabine in treating patients with advanced hematologic malignancies
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of 3-AP (Triapine) administered with high-dose cytarabine in patients with advanced hematologic malignancies. SECONDARY OBJECTIVES: I. Determine the clinical activity of this regimen in these patients. II. 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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
MTD defined as the dose preceding that at which greater than or equal to 2 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
Condition
Accelerated Phase Chronic Myelogenous Leukemia
Intervention
cytarabine
Study Arms / Comparison Groups
Treatment (cytarabine and triapine)
Description: Patients receive high-dose cytarabine IV over 2 hours on days 1-5 and 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
48
Start Date
January 2004
Primary Completion Date
July 2008
Eligibility Criteria
Inclusion Criteria: - 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 - Performance status - CALGB 0-2 - Performance status - Karnofsky 60-100% - No G6PD deficiency - Bilirubin < 2.0 mg/dL (unless due to Gilbert's syndrome) - AST and ALT < 2.5 times upper limit of normal (ULN) - Creatinine < 1.5 times ULN - No symptomatic congestive heart failure - No unstable angina pectoris - No cardiac arrhythmia - No pulmonary disease requiring oxygen - 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 - No concurrent biologic agents - 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 - At least 2 weeks since prior radiotherapy - No concurrent radiotherapy - 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Olatoyosi Odenike, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00077181
Organization ID
NCI-2012-02570
Secondary IDs
UCCRC-12806B
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Olatoyosi Odenike, Principal Investigator, University of Chicago Comprehensive Cancer Center
Verification Date
January 2013