VNP40101M and Cytarabine in Treating Patients With Hematologic Malignancies

NCT ID: NCT00070538

Last Updated: 2013-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2008-01-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as VNP40101M and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining VNP40101M with cytarabine in treating patients who have hematologic malignancies, including myelodysplastic syndrome or relapsed, refractory, or untreated leukemia.

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of VP40101M when administered with cytarabine in patients with hematologic malignancies.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of VNP40101M.

Patients receive cytarabine IV over 24 hours on days 1-4 for patients under 65 years of age OR on days 1-3 for patients 65 years of age and over. Patients also receive VNP40101M IV over 15-60 minutes on day 2. Treatment repeats every 4 weeks for up to 3 courses (in patients with responding disease) in the absence of disease progression or unacceptable toxicity. Patients with a continued response may receive additional courses at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of VNP40101M 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. Up to 10 patients may receive treatment at the MTD.

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

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cytarabine

Intervention Type: DRUG

laromustine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of leukemia or myelodysplastic syndromes (MDS) meeting criteria for 1 of the following:

• Relapsed or refractory leukemia for which there is no standard therapy anticipated to result in a durable remission

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myelogenous leukemia

• In blast crisis
• Untreated leukemia and standard therapy is refused
• Any of the following poor-risk MDS:

• Refractory anemia with excess blasts (RAEB)
• RAEB in transformation
• Chronic myelomonocytic leukemia
• CNS leukemia allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT or AST no greater than 3 times ULN
• Chronic hepatitis allowed

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No active heart disease
• No myocardial infarction within the past 3 months
• No symptomatic coronary artery disease
• No arrhythmias uncontrolled by medication
• No uncontrolled congestive heart failure

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No persistent chronic toxic effects from prior chemotherapy greater than grade 1
• No uncontrolled active infection

• Infections under control and under active treatment with antibiotics allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 48 hours since prior hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 2 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressing disease)
• No other concurrent standard or investigational treatment for leukemia
• No concurrent disulfiram

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vion Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Principal Investigators

Mario Sznol, MD

Role: STUDY_CHAIR

Vion Pharmaceuticals

Locations

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Giles F, Verstovsek S, Thomas D, Gerson S, Cortes J, Faderl S, Ferrajoli A, Ravandi F, Kornblau S, Garcia-Manero G, Jabbour E, O'Brien S, Karsten V, Cahill A, Yee K, Albitar M, Sznol M, Kantarjian H. Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia. Clin Cancer Res. 2005 Nov 1;11(21):7817-24. doi: 10.1158/1078-0432.CCR-05-1070.

Reference Type: RESULT

PMID: 16278404 (View on PubMed)

Giles FJ, Verstovsek S, Cortes J, et al.: Phase I study of VNP40101M (101M) and AraC in patients (pts) with refractory leukemia. [Abstract] J Clin Oncol 22 (14 Suppl): A-6617, 586s, 2004.

Reference Type: RESULT

Other Identifiers

CDR0000334879

Identifier Type: REGISTRY

Identifier Source: secondary_id

MDA-2003-0326

Identifier Type: -

Identifier Source: secondary_id

VION-CLI-034

Identifier Type: -

Identifier Source: org_study_id