3-AP and Cytarabine in Treating Patients With Hematologic Cancer - Full Text View

Sponsor:	Vion Pharmaceuticals
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00064090

Purpose

RATIONALE: Drugs used in chemotherapy such as cytarabine use different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth and may help cytarabine kill more cancer cells by making them more sensitive to the drug.

PURPOSE: Phase I trial to study the effectiveness of combining cytarabine with 3-AP in treating patients who have relapsed or refractory hematologic cancer.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: cytarabine Drug: triapine	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of Triapine and Cytarabine in Patients With Hematologic Malignancies

Resource links provided by NLM:

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

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

U.S. FDA Resources

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

Study Start Date:	March 2003
Primary Completion Date:	September 2004 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the feasibility, tolerability, and toxic effects of 3-AP in combination with cytarabine in patients with hematologic malignancies.
Determine the maximum tolerated dose and phase II dose of cytarabine in this regimen in these patients.
Determine the biological effects of 3-AP and its interaction with cytarabine in these patients.

OUTLINE: This is a pilot, dose-escalation study of cytarabine.

Patients receive 3-AP IV over 6 hours followed by cytarabine IV over 18 hours on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a response may receive an additional course as consolidation therapy.

Cohorts of 3-6 patients receive escalating doses of cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients receive treatment at that dose.

PROJECTED ACCRUAL: Approximately 20-25 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following hematologic malignancies:
- Acute myeloid leukemia
- Acute lymphoblastic leukemia
- Chronic myelogenous leukemia (CML)
- CML in blast crisis
- Chronic lymphocytic leukemia
- High-risk* myelodysplastic syndromes, including the following:
  - Refractory anemia with excess blasts (RAEB)
  - RAEB in transformation
  - Chronic myelomonocytic leukemia NOTE: *High-risk myelodysplasia defined as having an International Performance Scoring System score of at least 1.5, based on adverse cytogenetics, greater than 10% blasts in marrow, and cytopenias in at least 2 lineages
Relapsed or refractory disease
Ineligible for higher priority protocols

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

More than 2 months

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin no greater than 2.0 mg/dL (unless considered due to malignancy)
ALT or AST no greater than 3 times upper limit of normal
Chronic hepatitis allowed

Renal

Creatinine no greater than 2.0 mg/dL (unless considered due to malignancy)

Cardiovascular

No myocardial infarction within the past 3 months
No symptomatic coronary artery disease
No arrhythmias (other than atrial fibrillation or flutter) requiring treatment
No uncontrolled congestive heart failure

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Concurrent infections under active treatment with and controlled by antibiotics allowed
No other concurrent life-threatening illness
No mental deficit or psychiatric history that would preclude giving informed consent or complying with protocol

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 1 week since prior growth factors, including the following:
- Epoetin alfa
- Filgrastim (G-CSF)
- Sargramostim (GM-CSF)
- Interleukin-3
- Interleukin-11
No concurrent anticancer immunotherapy

Chemotherapy

At least 72 hours since prior hydroxyurea
Recovered from prior chemotherapy
No other concurrent anticancer chemotherapy

Endocrine therapy

Not specified

Radiotherapy

At least 2 weeks since prior radiotherapy
No concurrent anticancer radiotherapy

Surgery

Not specified

Other

At least 3 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressing disease)
At least 1 week since prior nonmyelosuppressive therapy
No other concurrent standard or investigational therapy for the malignancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064090

Locations

United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4095

Sponsors and Collaborators

Vion Pharmaceuticals

Investigators

Study Chair:

Mario Sznol, MD

Vion Pharmaceuticals

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000306465, VION-CLI-032, MDA-DM-030096
Study First Received:	July 8, 2003
Last Updated:	August 23, 2008
ClinicalTrials.gov Identifier:	NCT00064090 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
blastic phase chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
relapsing chronic myelogenous leukemia
chronic myelomonocytic leukemia
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts

previously treated myelodysplastic syndromes
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
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)

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia
Preleukemia
Pathologic Processes
Syndrome
Therapeutic Uses

Cytarabine
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Bone Marrow Diseases
Myelodysplastic-Myeloproliferative Diseases

ClinicalTrials.gov processed this record on November 09, 2009