First-in-man study of CPX-351: a liposomal carrier containing cytarabine and daunorubicin in a fixed 5:1 molar ratio for the treatment of relapsed and refractory acute myeloid leukemia.

ABSTRACT:

Purpose

This phase I dose-escalation trial was performed to determine the maximum-tolerated dose, dose-limiting toxicities, and pharmacokinetics of CPX-351.

Patients and methods

CPX-351 induction was administered on days 1, 3, and 5 by 90-minute infusion to 48 relapsed or refractory patients with acute myeloid leukemia (AML) or high-risk myelodysplasia. Doses started at 3 units/m(2) with dose doublings in single-patient cohorts until a pharmacodynamic effect (treatment-related adverse events or reduction in bone marrow cellularity or blast count) was observed, followed by 33% escalations in three patient cohorts until dose-limiting toxicity (DLT) occurred.

Results

The maximum-tolerated dose was 101 units/m(2). DLTs consisted of hypertensive crisis, congestive heart fa

SUBMITTER: Feldman EJ 

PROVIDER: S-EPMC4520927 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature