Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Temozolomide and VNP40101M in Treating Patients With Relapsed or Refractory Leukemias

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over Pharmaceutical / Industry VION-CLI-036 CWRU-050419, NCT00098436

Objectives

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

Entry Criteria

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

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

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

Expected Enrollment

Approximately 25 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Vion Pharmaceuticals, Incorporated

Bonny Johnson, RN, MSN, Protocol chair		Ph: 203-672-4537

Registry Information
Official Title		A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies
Trial Start Date		2004-09-24
Trial Completion Date		2006-10-13
Registered in ClinicalTrials.gov		NCT00098436
Date Submitted to PDQ		2004-11-03
Information Last Verified		2008-08-22