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

Sponsors and Collaborators:	University of Chicago National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00077181

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Leukemia	Drug: cytarabine Drug: triapine	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine Cytarabine hydrochloride 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of Triapine in Combination With High Dose Ara-C (Hi-DAC) in Patients With Advanced Hematologic Malignancies

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	December 2003
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of 3-AP (Triapine®) administered with high-dose cytarabine in patients with advanced hematologic malignancies.

Secondary

Determine the clinical activity of this regimen in these patients.
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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

CALGB 0-2 OR
Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

No G6PD deficiency

Hepatic

Bilirubin < 2.0 mg/dL (unless due to Gilbert's syndrome)
AST and ALT < 2.5 times upper limit of normal (ULN)

Renal

Creatinine < 1.5 times ULN

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Pulmonary

No pulmonary disease requiring oxygen

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent biologic agents

Chemotherapy

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

Endocrine therapy

Not specified

Radiotherapy

At least 2 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery

Not specified

Other

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00077181

Locations

United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470

Sponsors and Collaborators

University of Chicago

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Olatoyosi M. Odenike, MD

University of Chicago

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

Odenike OM, Larson RA, Gajria D, Dolan ME, Delaney SM, Karrison TG, Ratain MJ, Stock W. Phase I study of the ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde-thiosemicarbazone (3-AP) in combination with high dose cytarabine in patients with advanced myeloid leukemia. Invest New Drugs. 2008 Jun;26(3):233-9. Epub 2008 Jan 24.

Study ID Numbers:	CDR0000349659, UCCRC-12806B, NCI-6283
Study First Received:	February 10, 2004
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00077181
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
secondary acute myeloid leukemia

adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)

Study placed in the following topic categories:

Blast Crisis
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chronic myelogenous leukemia
Hematologic Neoplasms
Hematologic Diseases
Acute myelogenous leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Recurrence

Acute lymphoblastic leukemia, adult
Leukemia
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasm Metastasis
Acute myeloid leukemia, adult
Congenital Abnormalities
Acute myelocytic leukemia
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents

Physiological Effects of Drugs
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses

ClinicalTrials.gov processed this record on January 15, 2009