Dataset Information

A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias.

ABSTRACT:

Purpose

Daunorubicin can induce left ventricular dysfunction and QT interval prolongation. This study assessed the effects of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, on cardiac repolarization.

Methods

Twenty-six adults with acute leukemia were treated with CPX-351 for 1-2 induction cycles and ≤ 4 consolidation cycles. The primary endpoint was mean change in QTcF from baseline.

Results

Mean QTcF changes were < 10 ms at all time points. No clinically meaningful effects on heart rate, QRS interval, PR interval, or QTcB were observed. Estimated mean half-lives for total cytarabine and daunorubicin were > 30 h. Thirteen (50%) patients achieved remission. The most common adverse events were febrile neutropenia, fatigue, and nausea.

Conclusions

The cytarabine and daunorubicin in CPX-351 liposomes were metabolized and excreted similarly to conventional formulation; however, plasma pharmacokinetics were altered. CPX-351 did not prolong the QT interval, suggesting that CPX-351 may induce less cardiotoxicity than previously reported for conventional daunorubicin.

Trial registration

Clinicaltrials.gov identifier: NCT02238925.

SUBMITTER: Lin TL

PROVIDER: S-EPMC6562048 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias.

Lin Tara L TL Newell Laura F LF Stuart Robert K RK Michaelis Laura C LC Rubenstein Eric E Pentikis Helen S HS Callahan Timothy T Alvarez Donna D Liboiron Barry D BD Mayer Lawrence D LD Wang Qi Q Banerjee Kamalika K Louie Arthur C AC

Cancer chemotherapy and pharmacology 20190516 1

<h4>Purpose</h4>Daunorubicin can induce left ventricular dysfunction and QT interval prolongation. This study assessed the effects of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, on cardiac repolarization.<h4>Methods</h4>Twenty-six adults with acute leukemia were treated with CPX-351 for 1-2 induction cycles and ≤ 4 consolidation cycles. The primary endpoint was mean change in QTcF from baseline.<h4>Results</h4>Mean QTcF changes were < 10 ms at all time points. No clinicall ...[more]

PMID: 31098682

Similar Datasets

Project description:BackgroundLAMVYX was a multicenter, single-arm, phase 2 trial designed to validate the safety and efficacy of CPX-351 in patients aged 60-75 years with newly diagnosed, secondary acute myeloid leukemia and to generate evidence on key issues not addressed in the preceding regulatory pivotal trial.MethodsThe primary end point of the study was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate after induction. Eligible patients were recommended to undergo allogeneic hematopoietic stem cell transplantation after the first consolidation cycle. Alternatively, patients could undergo up to six maintenance cycles with CPX-351.ResultsTwenty-nine patients (49%; 95% exact confidence interval [CI], 37%-62%) patients achieved a CR/CRi after one or two cycles of induction, with a measurable residual disease negativity rate of 67% as assessed by centralized, multiparameter flow cytometry. Among patients who had serial next-generation sequencing analyses available, clearance of somatic mutations that were present at diagnosis was achieved in 7 (35%). The median follow-up among survivors was 16.8 months (range, 8.7-24.3 months). The median event-free survival was 3.0 months (95% CI, 1.4-7.3 months), and the median overall survival was 7.4 months (95% CI, 3.7-12.7 months). In landmark analyses at day +100 from diagnosis, the 1-year overall and event-free survival rate among patients who underwent allogeneic hematopoietic stem cell transplantation was 70% (95% CI, 47%-100%) and 70% (95% CI, 47%-100%), respectively. The corresponding values were 89% (95% CI, 71%-100%) and 44% (95% CI, 21%-92%), respectively, for patients who entered the maintenance phase. No significant longitudinal changes were observed in severity index or quality-of-life visual analog scale scores.ConclusionsThe current data provide novel insights that might inform the clinical positioning and optimal use of CPX-351, complementing previous results (ClinicalTrials.gov identifier NCT04230239).

Dataset Information

A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias.

Purpose

Methods

Results

Conclusions

Trial registration

Publications

A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets