Temozolomide and VNP40101M in Treating Patients With Relapsed or Refractory Leukemias

Sponsor

Vion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00098436

Collaborator

(none)

Enrollment

Locations

Duration (Months)

6.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temozolomide may also help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug. Giving temozolomide together with VNP40101M may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide and VNP40101M in treating patients with relapsed or refractory leukemias.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: laromustine Drug: temozolomide	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of temozolomide and VNP40101M in patients with relapsed or refractory leukemias.
Determine the toxic effects of this regimen in these patients.

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

Patients receive oral temozolomide twice daily on days 1-3 (for 5 doses) followed by VNP401010M IV over 15-60 minutes on day 3 (course 1). Patients achieving a complete or partial response or having ≥ 50% reduction in bone marrow blasts may receive a second course of therapy no earlier than day 43. Courses may be repeated approximately every 6 weeks at the discretion of the sponsor and in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of temozolomide until a dose that depletes leukemic blast AGT in at least 4 of 6 patients is determined. Once this dose is determined, cohorts of 3-6 patients receive escalating doses of VNP401010M 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 are treated at the MTD.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies

Study Start Date :

Sep 1, 2004

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Aug 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 1 of the following:
Acute myeloid leukemia
Acute lymphoblastic leukemia
Chronic myelogenous leukemia in blast crisis
Relapsed or refractory disease
No known standard therapy that is anticipated to result in a durable remission exists
CNS leukemia allowed

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT or AST ≤ 3 times ULN
Chronic hepatitis allowed

Renal

Creatinine ≤ 2.0 mg/dL

Cardiovascular

No active heart disease, including any of the following:
Myocardial infarction within the past 3 months
Symptomatic coronary artery disease
Arrhythmias not controlled by medication
Uncontrolled congestive heart failure

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
No uncontrolled active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Concurrent hydroxyurea allowed within the first 10 days of study drug administration for control of elevated blast levels or platelet counts
Maximum hydroxyurea dose 5 g daily
No persistent chronic toxic effects from prior chemotherapy > grade 1

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

Recovered from all prior therapy
At least 2 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressive disease)
No more than 2 leukapheresis procedures within the first 10 days of study drug administration for control of elevated blast levels or platelet counts
No concurrent disulfiram
No other concurrent anticancer drugs
No other concurrent standard or investigational treatment for leukemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	American Health Network - North Illinois Street	Indianapolis	Indiana	United States	46202
2	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
3	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
4	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195