A Phase I And Pharmacological Trial Of 17-Allylamino -17-demethoxygeldanamycin (17-AAG) And Cytarabine In Refractory Leukemia And Myelodysplastic Syndrome
I. Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
(tanespimycin) when administered with cytarabine in patients with relapsed or refractory
acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic
myelomonocytic leukemia, or high-grade myelodysplastic syndromes.
II. Determine the toxic effects of this regimen in these patients. III. Determine,
preliminarily, the activity of this regimen in these patients. IV. Correlate the
pharmacokinetics of this regimen with cytochrome p450 3A5 genotype in these patients.
V. Determine the effect of this regimen on client proteins in vivo and ex vivo using
leukemic blasts from patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of tanespimycin.
Patients receive induction therapy comprising cytarabine intravenously (IV) continuously on
days 1-5 and tanespimycin IV over 1 hour on days 3 and 6.
Patients achieving a morphologic complete response with incomplete blood count recovery
(CRi) or partial response may be eligible to receive a second induction course of therapy
after day 21 at the discretion of the principal investigator. Patients achieving a complete
response (CR) receive up to 4 courses of consolidation therapy with cytarabine and
tanespimycin. Consolidation therapy repeats approximately every 60 days in the absence of
disease progression or unacceptable toxicity. Patients who achieve CR and remain in
remission for ≥ 6 months may be retreated with cytarabine and tanespimycin (at the current
dose level or the maximum tolerated dose [MTD]) at the time of relapse. Cohorts of 3-6
patients receive escalating doses of tanespimycin until the 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. Patients are followed at 3 months.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Tolerability of tanespimycin with cytarabine in patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic myelomonocytic leukemia, or high-grade myelodysplastic syndromes
Evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 standard toxicity grading.
United States: Food and Drug Administration
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