Clinical trial NCT05828589: A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies
Official title: A Phase 1/1b Open-Label Dose-Escalation and Dose-Optimization Study of Bcl-2 Inhibitor BGB-21447 in Patients With Mature B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
Relapsed Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Relapsed Follicular Lymphoma
Relapsed Marginal Zone Lymphoma
Relapse Diffuse Large B Cell Lymphoma
Relapsed Small Lymphocytic Lymphoma
Refractory Follicular Lymphoma
Refractory Marginal Zone Lymphoma
Refractory Small Lymphocytic Lymphoma
Richter Transformation
Refractory Diffuse Large B-cell Lymphoma
Transformed Non-Hodgkin Lymphoma
Keywords: Relapsed Non-Hodgkin Lymphoma
refractory non-Hodgkin lymphoma
Relapsed Chronic Lymphocytic Leukemia
Follicular Lymphoma
Marginal Zone Lymphoma
NHL
FL
MZL
Refractory Chronic Lymphocytic Leukemia
RCLL
Relapsed Follicular Lymphoma
Refractory Follicular Lymphoma
Relapsed Marginal Zone Lymphoma
Refractory Marginal Zone Lymphoma
RFL
RMZL
Relapsed Small Lymphocytic Lymphoma
Refractory Small Lymphocytic Lymphoma
RSLL
Richter's transformation
RT
RR DLBCL
Bcl-2
Bcl-2i
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2023-04-25
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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."


Eligibility criteria: 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 (for Cohort A1 and Cohort A2.1)

      * High-grade B-cell lymphomas with translocations of MYC and Bcl-2 and/or Bcl-6 are not allowed in Cohort A1 but may be allowed in Cohort A2.1
   2. R/R FL (for Cohort A1 and Cohort A2.2)
   3. R/R MZL (for Cohort A1 and Cohort A2.2)
   4. Transformed B-cell NHL (for Cohort A1 only)
   5. Richter's transformation to DLBCL (for Cohort A1 only)
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 or lentigo maligna melanoma that has been curatively resected
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 protocol-defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Part 1: Number of participants with dose limiting toxicities (DLTs)
timeFrame: Up to approximately 1 month
measure: Number of participants with adverse events (AEs)
timeFrame: 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
measure: Number of participants with Tumor Lysis Syndrome (TLS)
timeFrame: 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
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) After a Single Dose of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: 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
timeFrame: Up to approximately 8 weeks
measure: Area under the curve from time 0 extrapolated to infinity time (AUCinf) After a Single Dose of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Time to reach maximum observed plasma concentration (Tmax) After a Single Dose of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Apparent terminal elimination half-life (t1/2) After a Single Dose of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Apparent oral clearance (CL/F) After a Single Dose of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Apparent volume of distribution (Vz/F) After a Single Dose of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Steady state maximum observed plasma concentration (Cmax,ss) of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Steady state pre-dose trough concentration (Ctrough,ss) of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Steady state area under the curve from time 0 to the quantifiable concentration (AUClast,ss) of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Steady state time to reach maximum observed plasma concentration (Tmax,ss) of BGB-21447
timeFrame: Up to approximately 8 weeks
measure: Overall response rate (ORR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Time to response (TTR)
timeFrame: Up to approximately 24 months
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Waukee
country: United States
facility: Mission Cancer and Blood
state: Iowa
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer At Johns Hopkins
state: Maryland
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center At Nyu Langone Health
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institue
state: South Dakota
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Yichang
country: China
facility: Yichang Central Peoples Hospitaljiangnan Branch
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Xianghu
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Peoples Hospital
state: Shandong
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Hospital of Blood Disease
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Dijon
country: France
facility: Chu Dijon
city: Montpellier
country: France
facility: Chu Montpellier Hopital Saint Eloi
city: Paris
country: France
facility: Hopital Saint Louis
city: Toulouse
country: France
facility: Iuc Toulouse Oncopole
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G Pascale
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Centroricerche Cliniche Di Verona Srl
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: