Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
B-cell lymphoma 2 inhibitor (BCL-2i), CLL-RR1, German CLL Study Group
Brief summary
The goal of this study is to compare how well sonrotoclax plus obinutuzumab works versus venetoclax plus rituximab in treating adults with relapsed and/or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study will also compare how well sonrotoclax plus rituximab works versus venetoclax plus rituxumab in treating adults with R/R CLL/SLL. The safety of these treatments will also be assessed.
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
DRUGSonrotoclax
Administered orally
DRUGObinutuzumab
Administered intravenously
DRUGRituximab
Administered intravenously
DRUGVenetoclax
Administered Orally
Sponsors
BeOne Medicines
German CLL Study Group
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
* Confirmed diagnosis of CLL/SLL that meets the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria * Received one or more prior therapies for CLL/SLL. For each line of therapy, participants must have received at least 2 cycles of the therapy * Participants with prior BCL2i exposure are eligible if remission duration was ≥3 years with ≥2 years from last BCL2i intake * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 * Adequate organ function
Exclusion criteria
* Known active prolymphocytic leukemia or currently suspected Richter's transformation * Prior autologous stem cell transplantation or chimeric antigen receptor T-cell therapy within 3 months before first dose of study drug * Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent * Known central nervous system involvement by CLL/SLL * Severe or debilitating pulmonary disease * Clinically significant cardiovascular disease NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as assessed by Blinded Independent Review Committee (BIRC) for Arm A versus Arm D | Up to approximately 51 months | PFS is defined as the time from randomization to the date of progression or death, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as assessed by BIRC for Arm B versus Arm D | Up to approximately 69 months | PFS is defined as the time from randomization to the date of progression or death, whichever occurs first. |
| Rate of uMRD4 for Arm A versus Arm D | Up to approximately 12 months | The rate of undetectable minimal residual disease (uMRD4) in peripheral blood based on next-generation sequencing (NGS) |
| Complete Response Rate as assessed by BIRC for Arm A versus Arm D | Up to approximately 25 months | Complete Response Rate (CRR) is defined as the percentage of participants that achieve a best response of complete response (CR) or complete response with incomplete hematopoietic recovery (CRi) |
| Overall Survival for Arm A versus Arm D | Up to approximately 84 months | Overall survival (OS) is defined as the time from the date of randomization to the date of death |
| PFS per Investigator Assessment (INV) for Arm B versus Arm D | Up to approximately 69 months | PFS is defined as the time from randomization to the date of progression or death, whichever occurs first. |
| CRR per BIRC and by INV for Arm B versus Arm D | Up to approximately 25 months | CRR is defined as the percentage of participants that achieve a best response of CR or CRi |
| OS for Arm B versus Arm D | Up to approximately 84 months | OS is defined as the time from the date of randomization to the date of death |
| Rate of uMRD4 for Arm B versus Arm D | Up to approximately 25 months | The rate of uMRD4 in peripheral blood based on NGS |
| PFS per BIRC and by INV for Arm A versus Arm B | Up to approximately 69 months | PFS is defined as the time from randomization to the date of progression or death, whichever occurs first. |
| CRR per BIRC and by INV for Arm A versus Arm B | Up to approximately 25 months | CRR is defined as the percentage of participants that achieve a best response of CR or CRi |
| OS for Arm A versus Arm B | Up to approximately 84 months | OS is defined as the time from the date of randomization to the date of death |
| Rate of uMRD4 for Arm A versus Arm B | Up to approximately 25 months | The rate of uMRD4 in peripheral blood based on NGS |
| CRR per INV for Arm A versus Arm D | Up to approximately 25 months | CRR is defined as the percentage of participants that achieve a best response of CR or CRi |
| PFS per INV for Arm A versus Arm D | Up to approximately 51 months | PFS is defined as the time from randomization to the date of progression or death, whichever occurs first. |
| PFS per INV for Arm C versus Arm D | Up to approximately 69 months | PFS is defined as the time from randomization to the date of progression or death, whichever occurs first. |
| CRR per INV for Arm C versus Arm D | Up to approximately 25 months | CRR is defined as the percentage of participants that achieve a best response of CR or CRi |
| OS for Arm C versus Arm D | Up to approximately 84 months | OS is defined as the time from the date of randomization to the date of death |
| Rate of uMRD4 for Arm C versus Arm D | Up to approximately 25 months | The rate of uMRD4 in peripheral blood based on NGS |
| Overall Response Rate (ORR) per BIRC and by INV | Up to approximately 25 months | ORR is defined as the percentage of participants that achieve a best response of partial response (PR) or better |
| Duration of Response (DOR) per BIRC and by INV | Up to approximately 69 months | DOR is defined as the time from the date that response criteria were first met to the date of first documentation of disease progression or death, whichever occurs first |
| Time to Response (TTR) per BIRC and by INV | Up to approximately 25 months | TTR is defined as the time from the date of randomization to the date response criteria were first met |
| Time to Next Anti-CLL/SLL Treatment (TTNT) | Up to approximately 84 months | TTNT is defined as the time from the date of randomization to the date of next anti-CLL/SLL treatment |
| Rate of uMRD4 | Up to approximately 25 months | The rate of uMRD4 in peripheral blood based on NGS |
| Change from Baseline in the European Organisation of Research and Treatment of Cancer-Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Global Health Status/Quality of Life and Physical Functioning Scales | Baseline and up to approximately 69 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 global health status (GHS) and functional scales indicate better health-related quality of life (HRQoL). |
| Change from Baseline in EORTC QLQ for Chronic Lymphocytic Leukemia (EORTC QLQ-CLL17) Symptom Burden and Fatigue Scales | Baseline and up to approximately 69 months | The EORTC QLQ-CLL17 is the CLL module of QLQ-C30 consisting of 17 items and comprising 3 scales: symptom burden due to disease and/or treatment (6 items), physical condition/fatigue (4 items), and worries/fears about health and functioning (7 items) Items are 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. Lower scores indicate better HRQoL. |
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | From the first dose of study drug(s) to 30 days after the last dose of sonrotoclax or venetoclax, or 90 days after the last dose of obinutuzumab or rituximab; up to approximately 26 months | Number of participants with TEAEs, including laboratory values, vital signs, and physical examination findings, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Ireland, Italy, Netherlands, New Zealand, Poland, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed