VNP40101M and Cytarabine in Treating Patients With Hematologic Malignancies

Sponsor

Vion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00070538

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: cytarabine Drug: laromustine	Phase 1

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Of VNP40101M And Cytarabine For Patients With Hematologic Malignancies

Study Start Date :

Jun 1, 2003

Actual Primary Completion Date :

Sep 1, 2004

Actual Study Completion Date :

Jan 1, 2008

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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