Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
CLL, SLL, BTK-targeted protein degrader
Brief summary
The purpose of this study is to investigate the efficacy and safety of BGB-16673 compared with investigator's choice (bendamustine plus rituximab or high-dose methylprednisolone plus rituximab) in participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously exposed to covalent Bruton tyrosine kinase inhibitor(s) (cBTKi).
Detailed description
Chronic lymphocytic leukemia and small lymphocytic lymphoma are types of blood cancer that affects people around the world. People with CLL and SLL suffer from enlarged lymph nodes, spleen, or liver, or have symptoms like night sweats, weight loss and fever. They have shorter life expectancy compared to healthy people. There is an urgent need for new treatment to prolong life and control disease-related symptoms. In this study, participants with R/R CLL or SLL who were previously exposed to a covalent BTKi will receive BGB-16673 or the investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab. The main purpose of this study is to compare the length of time that participants live without their CLL or SLL worsening between those participants who receive BGB-16673 versus the investigator's choice of treatment. Approximately 150 participants will be included in this study in Mainland China and Taiwan. Participants will be randomly allocated to receive either BGB-16673 or the investigator's choice of treatment.
Interventions
DRUGBGB-16673
Administered orally
DRUGBendamustine
Administered intravenously
DRUGRituximab
Administered intravenously
DRUGMethylprednisolone
Administered intravenously
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of CLL/SLL, requiring treatment, based on 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria. 2. Previously received treatment for CLL/SLL with a covalent BTKi. 3. Measurable disease by computer tomography/magnetic resonance imaging for patients with SLL. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 5. Adequate bone marrow function 6. Adequate kidney and liver function 7. Adequate blood clotting function
Exclusion criteria
1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation 2. 2\. Prior autologous stem cell transplant (unless ≥ 3 months after transplant) or chimeric antigen receptor-T cell (unless ≥ 6 months after cell infusion) 3. History of severe allergic reactions or hypersensitivity to the active ingredient and excipients of study treatment (BGB-16673, bendamustine, or rituximab) 4. Current or history of central nervous system involvement 5. History of ischemic stroke or intracranial hemorrhage within 6 months before first dose of study drug 6. History of confirmed progressive multifocal leukoencephalopathy. 7. Active fungal, bacterial, and/or viral infection requiring parenteral systemic therapy 8. Clinically significant cardiovascular disease NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) by IRC | Approximately 23 Months | PFS is defined as time from the date of randomization to the date of first disease progression or death, whichever occurs first, as determined by IRC using modified 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for participants with R/R CLL and the Lugano Classification for patients with R/R SLL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately 21 Months | OS is defined as time from the date of randomization to the date of death due to any cause. |
| Overall Response Rate (ORR) by IRC and Investigator Assessment | Approximately 23 Months | ORR is defined as the percentage of participants with best overall response of complete response (CR), complete response with incomplete bone marrow recovery (Cri), nodular partial remission (nPR), or partial response (PR) as assessed by the IRC or by the investigator. |
| Rate of Partial Response with Lymphocytosis (PR-L) or Higher Determined by Investigator Assessment | Approximately 23 Months | Rate of PR-L or higher is defined as the percentage of participants with a best overall response of complete response (CR), complete response with incomplete bone marrow recovery (Cri), nodular partial remission (nPR), partial response (PR), or partial response with lymphocytosis (PR-L) as assessed by the Investigator. |
| Duration of Response (DOR) by IRC and Investigator Assessment | Approximately 9 Months | DOR is defined as the time from initial response to disease progression or death, whichever occurs first, as assessed by the IRC or by the investigator. |
| PFS as Assessed by the Investigator | Approximately 12 Months | PFS is defined as time from the date of randomization to the date of first disease progression or death, whichever occurs first, as determined by the investigator using modified 2018 iwCLL criteria for participants with CLL and the Lugano Classification for patients with R/R SLL. |
| Time to Next Anti-CLL/SLL Treatment (TTNT) | Approximately 14 Months | TTNT is defined as the time from the date of randomization to the date of next anti-CLL/SLL treatment. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Approximately 14 Months | Safety will be assessed by monitoring and recording of all treatment emergent adverse events (AEs) and laboratory abnormalities graded by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. |
| Change from baseline in European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) Symptom Burden and Physical Condition Scales | Baseline and up to approximately 23 Months | The symptom burden and physical condition will be measured by QLQ-CLL17. EORTC QLQ-CLL17 comprises 17 items grouped into 3 multi-item scales: 1) symptom burden, 2) physical condition/fatigue, and 3) worries/fears about health and functioning. Each question is rated using a 4-point response scale (not at all, a little, quite a bit, and very much) and the recall period for all items is the past 7 days. The scores of each subscale are calculated based on the EORTC's protocol and then transformed to a 0 to 100 scale. Higher scores represent higher levels of symptom burden, physical condition/fatigue, or worries/fears about health and functioning. |
| Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire -Core 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) and Physical Functioning Scales | Baseline and up to approximately 23 Months | The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best). The scores of each subscale are calculated based on the EORTC's protocol and then transformed to a 0 to 100 scale. Higher scores in GHS and functional scales indicate better quality of life. |
| Time to Response (TTR) by IRC and Investigator Assessment | Approximately 6 Months | TTR is defined as the time from randomization until initial response, as assessed by the IRC or by the investigator. |
Countries
China, Taiwan
Contacts
Primary ContactStudy Director Study Director
Outcome results
None listed