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, Relapse Diffuse Large B Cell Lymphoma, Relapsed Marginal Zone Lymphoma, Relapsed Non-Hodgkin Lymphoma, Relapsed Small Lymphocytic Lymphoma, Richter Transformation, Transformed Non-Hodgkin Lymphoma
Conditions
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
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
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGBGB-21447
BGB-21447 will be administered orally
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Part 2: 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. |
Countries
Australia, China, New Zealand, United States
Contacts
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed