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


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

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 CenterDurham, North Carolina  27710
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
American Health Network - North Illinois StreetIndianapolis, Indiana  46202