Temozolomide and VNP40101M in Treating Patients With Relapsed or Refractory Leukemias
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.
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies|
|Study Start Date:||September 2004|
|Study Completion Date:||August 2008|
|Primary Completion Date:||October 2006 (Final data collection date for primary outcome measure)|
- 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.
|United States, Indiana|
|American Health Network - North Illinois Street|
|Indianapolis, Indiana, United States, 46202|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Study Chair:||Bonny L. Johnson, RN, MSN||Vion Pharmaceuticals|