A phase 1 trial of 8-chloro-adenosine in relapsed/refractory acute myeloid leukemia: An evaluation of safety and pharmacokinetics.

ABSTRACT:

Background

This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 8-chloro-adenosine (8-Cl-Ado) in patients with relapsed/refractory acute myeloid leukemia (AML).

Methods

8-Cl-Ado was administered daily for 5 days; the starting dose was 100 mg/m² , the highest dose tested was 800 mg/m² . The end points were toxicity, disease response, and PK/PD measurements.

Results

The predominant nonhematologic toxicity was cardiac with grade ≥3 toxicity. Plasma PK in all patients suggested heterogeneity among patients, yet, some dose-dependency for the accumulation of 8-Cl-Ado. Two 8-Cl-Ado metabolites accumulated at similar levels to 8-Cl-Ado. Cellular PK in eight patients indicated accumulation of 8-Cl-ATP, which was associated

SUBMITTER: Pullarkat V 

PROVIDER: S-EPMC11687610 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature