A Phase I Study Of VNP40101M And Cytarabine For Patients With Hematologic Malignancies
A Phase I Study Of VNP40101M And Cytarabine For Patients With Hematologic Malignancies
RATIONALE: Drugs used in chemotherapy, such as VNP40101M and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of combining VNP40101M with cytarabine in treating patients who have hematologic malignancies, including myelodysplastic syndrome or relapsed, refractory, or untreated leukemia.
OBJECTIVES:
OUTLINE: This is an open-label, dose-escalation study of VNP40101M.
Patients receive cytarabine IV over 24 hours on days 1-4 for patients under 65 years of age OR on days 1-3 for patients 65 years of age and over. Patients also receive VNP40101M IV over 15-60 minutes on day 2. Treatment repeats every 4 weeks for up to 3 courses (in patients with responding disease) in the absence of disease progression or unacceptable toxicity. Patients with a continued response may receive additional courses at the discretion of the investigator.
Cohorts of 3-6 patients receive escalating doses of VNP40101M 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 may receive treatment at the MTD.
PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Diagnosis of leukemia or myelodysplastic syndromes (MDS) meeting criteria for 1 of the following:
Relapsed or refractory leukemia for which there is no standard therapy anticipated to result in a durable remission
Acute myeloid leukemia
Acute lymphocytic leukemia
Chronic myelogenous leukemia
Untreated leukemia and standard therapy is refused
Any of the following poor-risk MDS:
CNS leukemia allowed
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No persistent chronic toxic effects from prior chemotherapy greater than grade 1
No uncontrolled active infection
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
Other