A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies
18 Years
N/A
Both
Leukemia
Trial Information
A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies
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.
Inclusion 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
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Bonny L. Johnson, RN, MSN
Investigator Role:
Study Chair
Investigator Affiliation:
Vion Pharmaceuticals
Authority:
United States: Federal Government
Study ID:
CDR0000405825
NCT ID:
NCT00098436
Start Date:
September 2004
Completion Date:
Related Keywords:
- Leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult acute lymphoblastic leukemia
- blastic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- secondary acute myeloid leukemia
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- Leukemia
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Case Comprehensive Cancer Center | Cleveland, Ohio 44106-5065 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| American Health Network - North Illinois Street | Indianapolis, Indiana 46202 |
