CLL, Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL
Brief summary
The purpose of this study is to investigate the efficacy and safety of BGB-16673 compared with investigator's choice (idelalisib plus rituximab \[for CLL only\] or bendamustine plus rituximab or venetoclax plus rituximab retreatment) in participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously exposed to both BTK inhibitors (BTKi) and BCL2 inhibitors (BCL2i).
Detailed description
Chronic lymphocytic leukemia is a type of blood cancer that affects people around the world. People with CLL 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 relapsed/refractory (R/R) CLL who were previously exposed to a BTKi and a BCL2i will receive BGB-16673 or the investigator's choice of idelalisib plus rituximab (for CLL only) or bendamustine plus rituximab or venetoclax plus rituximab retreatment. 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 (idelalisib plus rituximab or bendamustine plus rituximab, or venetoclax plus rituximab). Approximately 250 participants will be included in this study around the world. Participants will be randomly allocated to receive either BGB-16673 or the investigator's choice of treatment. "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-16673
Administered orally
DRUGBendamustine
Administered intravenously
DRUGIdelalisib
Administered orally
DRUGRituximab
Administered intravenously
DRUGVenetoclax
Administered orally
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 or SLL, requiring treatment, based on 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria. 2. Previously received treatment for CLL/SLL with both a BTKi and a BCL2i. 3. Participants with SLL must have measurable disease by computer tomography (CT)/magnetic resonance imaging (MRI) 4. Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2 5. Adequate liver function 6. Adequate blood clotting function
Exclusion criteria
1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation 2. Prior autologous stem cell transplant or chimeric antigen receptor-T cell therapy in the last 3 months 3. Known central nervous system involvement 4. Prior exposure to any BTK protein degraders 5. Active fungal, bacterial and/or viral infection requiring parenteral systemic therapy 6. Clinically significant cardiovascular disease NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) by Independent Review Committee (IRC) | Approximately 36 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 chronic lymphocytic leukemia (CLL) and Lugano classification for participants with small lymphocytic lymphoma (SLL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Next Anti-CLL/SLL Treatment (TTNT) | Approximately 36 Months | TTNT is defined as the time from the date of randomization to the date of next anti-CLL/SLL treatment. |
| Overall Survival (OS) | Approximately 36 Months | OS is defined as time from the date of randomization to the date of death due to any cause. |
| Progression-Free Survival (PFS) in Participants with Prior Exposure to Noncovalent Bruton Tyrosine Kinase Inhibitor(s) (ncBTKi) by IRC | Approximately 36 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 iwCLL for participants with prior exposure to ncBTKi. |
| PFS by the Investigator Assessment | Approximately 36 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 Lugano classification for participants with SLL |
| Overall Response Rate (ORR) by IRC and Investigator Assessment | Approximately 36 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 IRC and by Investigator Assessment | Approximately 36 Months | Rate of PR-L or higher is defined as the percentage of participants with a best overall response of CR, CRi, nPR, PR, or PR-L as assessed by the IRC or by the Investigator |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Approximately 36 Months | Safety will be assessed by monitoring and recording of all treatment emergent adverse events (AEs) graded by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. |
| 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/QoL (GHS) and Physical Functioning Scales | Approximately 24 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). Higher scores in GHS and functional scales indicate better quality of life. |
| Duration of Response (DOR) by IRC and Investigator Assessment | Approximately 36 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. |
| Change from baseline in EORTC Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) Symptom Burden and Physical Condition Scales | Approximately 24 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. |
Countries
Argentina, Australia, Brazil, Canada, Czechia, Germany, Italy, Japan, Netherlands, Poland, South Korea, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed