Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

Venetoclax has been approved in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. There are several clinical trials of Venetoclax for the treatment of AML. In trial M14-358 (NCT02203773), 91% of the combination of venetoclax and azacitidine were Caucasian, while about 87% of the the combination of Venetoclax and decitabine were Caucasian. In another trial M14-387 (NCT02287233), up to 94.9% of the combination of venetoclax and low-dose cytarabine group were Caucasian. However, the actual proportion of Asian or other races is unknown in both trials. Therefore, there is not enough data from Chinese other Asian races regarding its efficacy or adverse reactions in clinical trials. 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 most of the subjects were chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) or non-Hodgkin's lymphoma (NHL), and the results may not be directly generalized to AML patients. 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 cytopenia. About 40% of patients developed severe neutropenia, 4.7% required interruption of treatment, and 3.7% required dosage reduction in phase 2 clinical trials. Although no patient requires permanent venetoclax treatment discontinuation because of neutropenia, 9% of patients need to discontinue venetoclax treatment due to infection. The incidence of severe thrombocytopenia and anemia is 18% and 15%. Recent studies have found that the incidence of 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 incidence 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. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04613622
Study type Observational
Source National Taiwan University Hospital
Contact Shu-Wen Lin, Pharm.D
Phone 886-2-33668782
Email shuwenlin@ntu.edu.tw
Status Recruiting
Phase
Start date August 1, 2020
Completion date December 31, 2025

See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Recruiting NCT04460235 - Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma Phase 4
Completed NCT04022785 - PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Phase 1
Completed NCT03678493 - A Study of FMT in Patients With AML Allo HSCT in Recipients Phase 2
Recruiting NCT05424562 - A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
Completed NCT03197714 - Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia Phase 1
Terminated NCT03224819 - Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) Early Phase 1
Active, not recruiting NCT04070768 - Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113 Phase 1
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Active, not recruiting NCT04107727 - Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML) Phase 2
Recruiting NCT04920500 - Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients N/A
Recruiting NCT04385290 - Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC) Phase 1/Phase 2
Recruiting NCT03897127 - Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics Phase 3
Active, not recruiting NCT04021368 - RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Phase 1
Recruiting NCT03665480 - The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML Phase 2/Phase 3
Completed NCT02485535 - Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant Phase 1
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Recruiting NCT04069208 - IA14 Induction in Young Acute Myeloid Leukemia Phase 2
Recruiting NCT05744739 - Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML) Phase 1
Recruiting NCT04969601 - Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings Phase 1/Phase 2