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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00077181
First received: February 10, 2004
Last updated: January 23, 2013
Last verified: January 2013
History of Changes

February 10, 2004
January 23, 2013
January 2004
July 2008   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
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Complete list of historical versions of study NCT00077181 on ClinicalTrials.gov Archive Site
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3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies
A Phase I Study of Triapine in Combination With High Dose Ara-C (Hi-DAC) in Patients With Advanced Hematologic Malignancies

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

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.
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • Drug: cytarabine
    Given IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: triapine
    Given IV
    Other Names:
    • 3-AP
    • OCX-191
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: 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.
Interventions:
  • Drug: cytarabine
  • Drug: triapine
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
Not Provided
July 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00077181
NCI-2012-02570, UCCRC-12806B, U01CA069852, CDR0000349659
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Olatoyosi Odenike University of Chicago Comprehensive Cancer Center
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP