A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies

Refractory Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase 1/1b Open-Label Dose-Escalation Study of Bcl-2 Inhibitor BGB-21447 in Patients With Mature B-Cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05828589
• Other study ID #: BGB-21447-101
• Secondary ID: CT-2023-CTN-0542
• Status: Recruiting
• Phase: Phase 1
• Start date: June 20, 2023
• Est. completion date: October 2026

Study information

• Verified date: March 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: +1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 adminstered 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 Expansion."

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: October 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following:

Cohort A1 and Cohort A2:

1. R/R DLBCL

2. R/R FL

3. R/R MZL

4. Transformed B-cell NHL

5. Richter's transformation to DLBCL

2. Measurable disease by computed tomography/magnetic resonance imaging.

Exclusion Criteria:

1. 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

2. Known central nervous system involvement by lymphoma/leukemia

3. 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

4. Prior allogeneic stem cell transplant.

5. Major surgery < 4 weeks before the first dose of study treatment NOTE: Other Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Refractory Chronic Lymphocytic Leukemia
• Refractory Diffuse Large B-cell Lymphoma
• Refractory Follicular Lymphoma
• Refractory Marginal Zone Lymphoma
• Refractory Non-Hodgkin Lymphoma
• Refractory Small Lymphocytic Lymphoma
• Relapsed Chronic Lymphocytic Leukemia
• Relapsed Follicular Lymphoma
• Relapsed Non-Hodgkin Lymphoma
• Relapsed Small Lymphocytic Lymphoma
• Richter Transformation
• Transformed Non-Hodgkin Lymphoma

Intervention

Drug:
• BGB-21447
BGB-21447 will be administered orally

Locations

Country	Name	City	State
Australia	Linear Clinical Research	Nedlands	Western Australia
China	Peking University Third Hospital	Beijing	Beijing
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Shandong Provincial Hospital	Jinan	Shandong
China	Linyi Peoples Hospital	Linyi	Shandong
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Affiliated Zhongshan Hospital of Fudan University	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute of Hematology and Hospital of Blood Disease	Tianjin	Tianjin
China	Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of participants with dose limiting toxicities (DLTs)	Number of participants with dose limiting toxicities, defined as [see text in SAP or protocol for specific definition]	Up to approximately four years
Primary	Number of participants with adverse events (AEs)	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).	Up to approximately four years
Primary	Number of participants with Tumor Lysis Syndrome (TLS)	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.	Up to approximately four years
Secondary	Maximum observed plasma concentration (Cmax) of BGB-21447		Up to approximately four years
Secondary	Pre-dose trough concentration (Ctrough) of BGB-21447		Up to approximately four years
Secondary	Area under the curve from time 0 to the last sampling time point within the dose interval (AUClast) of BGB-21447		Up to approximately four years
Secondary	Area under the curve from time 0 extrapolated to infinity (AUCinf) of BGB-21447		Up to approximately four years
Secondary	Time to reach maximum observed plasma concentration (Tmax) of BGB-21447		Up to approximately four years
Secondary	Apparent terminal elimination half life (t1/2) of BGB-21447		Up to approximately four years
Secondary	Apparent oral clearance (CL/F) of BGB-21447		Up to approximately four years
Secondary	Apparent volume of distribution (Vz/F) of BGB-21447		Up to approximately four years
Secondary	Steady state maximum observed plasma concentration (Cmax) of BGB-21447		Up to approximately four years
Secondary	Steady state pre-dose trough concentration (Ctrough) of BGB-21447		Up to approximately four years
Secondary	Steady state area under the curve from time 0 to the last sampling time point within the dose interval (AUClast) of *drug name*		Up to approximately four years
Secondary	Steady state area under the curve from time 0 extrapolated to infinity (AUCinf) of BGB-21447		Up to approximately four years
Secondary	Steady state time to reach maximum observed plasma concentration (Tmax) of BGB-21447		Up to approximately four years
Secondary	Steady state apparent terminal elimination half life (t1/2) of BGB-21447		Up to approximately four years
Secondary	Steady state apparent oral clearance (CL/F) of BGB-21447		Up to approximately four years
Secondary	Steady state apparent volume of distribution (Vz/F) of BGB-21447		Up to approximately four years
Secondary	Overall response rate (ORR)	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	Up to approximately four years
Secondary	Duration of Response (DOR)	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.	Up to approximately four years
Secondary	Time to response (TTR)	defined as the time from treatment initiation to the first documentation of response.	Up to approximately four years
Secondary	Progression-free survival (PFS)	defined as the time from treatment initiation to the first documented disease progression or death due to any cause, whichever occurs first.	Up to approximately four years