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

Phase 1

Completed

• 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
• Interventions: Drug: cytarabine; Drug: triapine; Other: laboratory biomarker analysis

• Registration Number: NCT00077181
• Lead Sponsor: National Cancer Institute (NCI)

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 Timeline

• Study Start: 2004-01
• Study First Submitted: 2004-02-10
• Study First Submitted QC: 2004-02-10
• Study First Posted: 2004-02-11
• Primary Completion: 2008-07
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-23
• Last Update Posted: 2013-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (cytarabine and triapine)	cytarabine	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.
Treatment (cytarabine and triapine)	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.
Treatment (cytarabine and triapine)	laboratory biomarker analysis	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.

Primary Outcome Measures

Name	Time	Method
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	28 days

Trial Locations

Locations (1)

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States