A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered CNF1010 )17-(Allylamino)-17-Demethoxygeldanamycin [17-AAG]) in Patients With Gleevec-Resistent Chronic Myelogenous Leukemia
- Determine the maximum tolerated dose and dose-limiting toxicity of
17-N-allylamino-17-demethoxygeldanamycin (17-AAG), in terms of frequency, severity, and
duration of treatment-emergent adverse events, in patients with imatinib
mesylate-resistant Philadelphia chromosome (Ph)-positive chronic phase chronic
- Determine the pharmacokinetics of this drug and its primary metabolite
(17-amino-17-demethoxygeldanamycin) in these patients.
- Determine the hematologic response rate, in terms of WBC count, platelet count, and
assessment of blast cells in peripheral blood, in patients treated with this drug.
- Determine the cytogenic response rate, in terms of Ph-positive progenitor cells in the
bone marrow, in patients treated with this drug.
- Assess the effect of this drug on pharmacodynamic markers (i.e., CRKL phosphorylation,
BCR-ABL kinase activity, and BCR-ABL, RAF kinase, and HSP70 expression) in these
OUTLINE: This is an open label, dose-escalation, multicenter study.
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 15 minutes or 1
hour (depending on the dose administered) once on days 1, 4, 8, 11, 15, 18, 22, and 25.
Treatment repeats every 28 days for up to 3 courses in the absence of unacceptable toxicity
or disease progression. Eligible patients may receive additional courses of 17-AAG at the
discretion of the investigator.
Cohorts of 3-6 patients receive escalating doses of 17-AAG 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 additional patients are treated at the
Patients are followed for 1 month.
PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Charles Sawyers, MD
Jonsson Comprehensive Cancer Center
United States: Federal Government
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|