search
Back to results

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

Primary Purpose

Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cytarabine
triapine
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Accelerated Phase Chronic Myelogenous Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cytarabine and triapine)

Arm 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
February 10, 2004
Last Updated
January 23, 2013
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00077181
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
January 2004 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cytarabine and triapine)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
triapine
Other Intervention Name(s)
3-AP, OCX-191
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olatoyosi Odenike
Organizational Affiliation
University of Chicago Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs