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

NCT ID: NCT00077181

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31

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.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (cytarabine and triapine)

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.

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

Given IV

triapine

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

cytarabine

Given IV

Intervention Type: DRUG

triapine

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; 3-AP; OCX-191

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olatoyosi Odenike

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

UCCRC-12806B

Identifier Type: -

Identifier Source: secondary_id

U01CA069852

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000349659

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02570

Identifier Type: -

Identifier Source: org_study_id