A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies
- Conditions
- Refractory Chronic Lymphocytic LeukemiaRelapsed Non-Hodgkin LymphomaRefractory Non-Hodgkin LymphomaRelapsed Chronic Lymphocytic LeukemiaRelapsed Follicular LymphomaRelapsed Marginal Zone LymphomaRelapse Diffuse Large B Cell LymphomaRelapsed Small Lymphocytic LymphomaRefractory Follicular LymphomaRefractory Marginal Zone Lymphoma
- Interventions
- Registration Number
- NCT05828589
- Lead Sponsor
- BeiGene
- Brief Summary
This study is testing the safety and tolerability of BGB-21447 monotherapy in participants with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study aims to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), recommended Phase 2 dose (RP2D), and pharmacokinetic profile of the drug. Additionally, preliminary antitumor activity will be characterized. The study is divided into 2 main parts: Part 1 "Monotherapy Dose Finding" and Part 2 "Monotherapy Dose Optimization."
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 112
Not provided
- Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer or lentigo maligna melanoma that has been curatively resected
- Known central nervous system involvement by lymphoma/leukemia
- Prior autologous stem cell transplant < 3 months before the first dose of study drug. Or prior chimeric antigen receptor T-cell (CAR-T) therapy < 3 months before the first dose of study drug
- Prior allogeneic stem cell transplant.
- Major surgery < 4 weeks before the first dose of study treatment
NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 (Cohort A1): Dose escalation in patients with B-cell non-Hodgkin lymphoma (NHL) BGB-21447 Participants with R/R B-cell NHL (including diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], marginal zone lymphoma \[MZL\], transformed B-cell NHL (B-NHL), and Richter's transformation to DLBCL) will receive BGB-21447 once a day. Part 1 (Cohort B): Dose escalation in R/R CLL/SLL participants with low tumor burden BGB-21447 Participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive BGB-21447 once a day. Part 2 (Cohort A2.1): BGB-21447 Monotherapy Dose Optimization in R/R DLBCL BGB-21447 Participants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy. Part 2 (Cohort A2.2): BGB-21447 Monotherapy Dose Optimization in R/R FL or R/R MZL BGB-21447 Participants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy.
- Primary Outcome Measures
Name Time Method Part 1: Number of participants with dose limiting toxicities (DLTs) Up to approximately 1 month Number of participants with dose limiting toxicities, as defined in the study protocol.
Number of participants with adverse events (AEs) From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed and graded based upon the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
Number of participants with Tumor Lysis Syndrome (TLS) From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months TLS will be determined via laboratory values and assessed by the investigator.
In laboratory tumor lysis syndrome, 2 or more metabolic abnormalities must be present during the 24-hour period within 3 days before the start of study drug treatment or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac dysrhythmia, or death.
- Secondary Outcome Measures
Name Time Method Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-21447 Up to approximately 8 weeks Area under the curve from time 0 to the last sampling time point within the dose interval (AUC0-t) After a Single Dose of BGB-21447 Up to approximately 8 weeks Area under the curve from time 0 extrapolated to infinity time (AUCinf) After a Single Dose of BGB-21447 Up to approximately 8 weeks Time to reach maximum observed plasma concentration (Tmax) After a Single Dose of BGB-21447 Up to approximately 8 weeks Apparent terminal elimination half-life (t1/2) After a Single Dose of BGB-21447 Up to approximately 8 weeks Apparent oral clearance (CL/F) After a Single Dose of BGB-21447 Up to approximately 8 weeks Apparent volume of distribution (Vz/F) After a Single Dose of BGB-21447 Up to approximately 8 weeks Steady state maximum observed plasma concentration (Cmax,ss) of BGB-21447 Up to approximately 8 weeks Steady state pre-dose trough concentration (Ctrough,ss) of BGB-21447 Up to approximately 8 weeks Steady state area under the curve from time 0 to the quantifiable concentration (AUClast,ss) of BGB-21447 Up to approximately 8 weeks Steady state time to reach maximum observed plasma concentration (Tmax,ss) of BGB-21447 Up to approximately 8 weeks Overall response rate (ORR) Up to approximately 24 months Defined as the percentage of patients who achieve partial response or better for diffuse large B-cell lymphoma, marginal zone lymphoma, follicular lymphoma, transformed B-NHL, and Richter's transformation to DLBCL as per the Lugano Classification for non-Hodgkin lymphoma.
Duration of Response (DOR) Up to approximately 24 months Defined as the time from the first response documentation to the date that progression is documented after treatment initiation or death due to any cause, whichever occurs first.
Time to response (TTR) Up to approximately 24 months Defined as the time from treatment initiation to the first documentation of response.
Progression-free survival (PFS) Up to approximately 24 months Defined as the time from treatment initiation to the first documented disease progression or death due to any cause, whichever occurs first.
Trial Locations
- Locations (22)
Pindara Private Hospital
🇦🇺Benowa, Queensland, Australia
Mission Cancer and Blood
🇺🇸Waukee, Iowa, United States
Sidney Kimmel Comprehensive Cancer At Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Avera Cancer Institue
🇺🇸Sioux Falls, South Dakota, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
The First Affiliated Hospital of Nanchang University Branch Xianghu
🇨🇳Nanchang, Jiangxi, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Shandong Provincial Hospital
🇨🇳Jinan, Shandong, China
Linyi Peoples Hospital
🇨🇳Linyi, Shandong, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Institute of Hematology and Hospital of Blood Disease
🇨🇳Tianjin, Tianjin, China
Auckland City Hospital
🇳🇿Auckland, New Zealand