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

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase I Study of Triapine in Combination With High Dose Ara-C (Hi-DAC) in Patients With Advanced Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00077181
• Other study ID #: NCI-2012-02570
• Secondary ID: UCCRC-12806BU01C
• Status: Completed
• Phase: Phase 1
• First received: February 10, 2004
• Last updated: January 23, 2013
• Start date: January 2004

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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)
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Relapsing Chronic Myelogenous Leukemia
• Secondary Acute Myeloid Leukemia

Intervention

Drug:
• cytarabine
Given IV
• triapine
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes