NCT04616274

Pharmacokinetics of Venetoclax in Patients With Chronic Lymphocytic Leukemia

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 500 (estimated)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

Venetoclax is a treatment for chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, the pharmacokinetic data in Chinese population, as well as the change of venetoclax plasma concentration while taking CYP enzyme inducers or inhibitors, remained unknown so far. Therefore, the aim of this study is to investigate the pharmacokinetic characteristics of venetoclax.

Detailed description

Venetoclax has been approved for treatment of adult patients with chronic lymphocytic leukemia (CLL). Currently, there is not enough data of CLL populations from Chinese or other Asian regarding its efficacy or adverse reactions. In the phase 3 MURANO trial (NCT02005471), only 8 Asians (2.06%) were included, while other phase 1 or phase 2 studies did not show the percentage of Asian population. According to a venetoclax population pharmacokinetic study published in 2016, which integrated 505 subjects from 8 clinical trials, concluded that race was not a covariate that affect venetoclax PK. However, only 6 Asians (1.19%) were included, and some of the subjects were small lymphocytic lymphoma (SLL), non-Hodgkin's lymphoma (NHL) or healthy volunteers. The pharmacokinetics of venetoclax is affected by many factors, and the most influential factors may be fat content from dietary and concomitant use of CYP3A inhibitors or inducers. In particular, patients with hematological malignancies often require antifungal agents (such as voriconazole, posaconazole) as prophylaxis or treatment of fungal infections during chemotherapy. Therefore, these two factors will be considered in this study. The most common side effect after using venetoclax is neutropenia. About 60.8% of patients developed any grades neutropenia, 43.3% required dose interruption, 8.2% required dosage reduction, and 2.6% required permanent treatment discontinuation because of neutropenia in phase 3 MURANO trial. Recent studies have found that the probability of ≥ grade 3 neutropenia and infection seems to be inversely related to the blood concentration of venetoclax, that is, the higher the blood concentration of venetoclax, the lower the probability of neutropenia and infection. This observational study is designed to examine the plasma concentration of venetoclax in patients with CLL or AML, to create a pharmacokinetic model of venetoclax in Chinese population, and to analyze the extent to which CYP enzyme inhibitors and inducers may have effect on venetoclax plasma concentration. Moreover, the association between therapeutic effectiveness, adverse events, and venetoclax plasma concentration will also be analyzed in this study, and the final purpose is to establish the principle of clinical dose adjustment in the future.

Conditions

• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	Venetoclax	This prospective study will draw blood from every patient to measure the venetoclax blood concentration. After blood concentration analysis by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), the investigator will report the concentration to clinicians.

Timeline

• Start date: 2020-07-01
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2020-11-04
• Last updated: 2021-10-28

Locations

1 site across 1 country: Taiwan

Regulatory

• FDA-regulated drug study