Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL
Brief summary
The purpose of this study is to support the registration plan of sonrotoclax plus zanubrutinib treatment in participants with previously untreated chronic lymphocytic leukemia (CLL). This study is designed to assess the contribution of sonrotoclax to the efficacy outcome of the combination of zanubrutinib and sonrotoclax.
Detailed description
This study will test how effective and safe Sonrotoclax plus Zanubrutinib treatment compared with Zanubrutinib alone in participants with previously untreated chronic lymphocytic leukemia (CLL). The main goals of the study are to determine how many participants may no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment and to determine what adverse events, or side effects, patients might experience. Sonrotoclax is an experimental drug that works by blocking a protein called B-cell lymphoma-2 (Bcl-2). This protein helps certain types of blood tumor cells to survive and grow. When Sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with CLL disease. Zanubrutinib is a commercialized product that works by blocking a protein called Bruton's tyrosine kinase (BTK) and controlling the activity and survival of malignant B cells. Zanubrutinib has received approval in over 65 countries/regions worldwide for the treatment of adult participants with B cell malignancies, including CLL. The study will enroll approximately 87 participants who will be randomly assigned by a computer program to receive one of the following treatments: sonrotoclax + zanubrutinib or zanubrutinib. The study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 5 years. 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
DRUGZanubrutinib
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. Previously untreated adult patient ≥ 18 years with a confirmed diagnosis of CLL. 2. CLL requiring treatment as per pre-defined criteria. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0,1, or 2. 4. Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI). 5. Adequate marrow function. 6. Adequate liver function as indicated by aspartate aminotransferase (AST) alanine aminotransferase (ALT) and serum total bilirubin. 7. Adequate renal function. 8. Life expectancy \> 6 months. 9. Signed informed consent and able to comply with the study protocol in the investigator's judgment. 10. Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 90 days after the last dose of study drug.
Exclusion criteria
1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation 2. Known central nervous system involvement 3. Received previous systemic treatment for CLL 4. Clinically significant cardiovascular disease 5. Severe or debilitating pulmonary disease 6. History of prior malignancy 7. Active fungal, bacterial, and/or viral infection requiring systemic therapy 8. Positive human immunodeficiency virus (HIV) serology (HIVAb) status or serologic status reflecting active hepatitis B or C infection 9. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment 10. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 11. History of stroke or intracranial hemorrhage ≤ 6 months before the first dose of study treatment 12. Unable to swallow capsules or tablets or diseases significantly affecting GI function 13. Hypersensitivity to zanubrutinib, sonrotoclax, or any of its excipients 14. Use of investigational agents within the last 4 weeks before screening 15. Pregnant and lactating females Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR)/ Complete Response with Incomplete Bone Marrow Recovery (CRi) Rate | Month 16 | Best CR/CRi rate per the Independent Review Committee (IRC) response assessment using the 2018 International Workshop on Chronic Lymphocytic Leukemia guidelines with modification for treatment-related lymphocytosis for participants with CLL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Undetectable Minimal Residual Disease at < 10^-4Sensitivity (uMRD4) Rate | Month 16 | uMRD4 rate measured in both peripheral blood and bone marrow aspirate |
| CR/CRi Rate per Investigator Response Assessment | Month 16 | CR/CRi Rate (CRR) is defined as the percentage of participants with best overall response of CR or CRi |
| Overall Response Rate (ORR) per IRC and Investigator Response Assessment | Up to 66 Months | ORR is defined as the percentage of participants achieving overall response (CR+CRi+partial response \[PR\]+nodular PR) per the IRC and the investigator response assessment. |
| Duration of Response (DOR) per Investigator Response Assessment | Up to 66 Months | DOR is defined as the time from first qualifying response (PR, nodular PR, CR,or CRi) until CLL progression or death. |
| Time to Response (TTR) per IRC and Investigator Response Assessment | Up to 66 Months | TTR is defined as the time from treatment initiation to the first documentation of response |
| Landmark Progression-free Survival Rate at 24 Months per Investigator Assessment | 24 Months | The 24-month landmark PFS rate is defined as the percentage of participants who remain alive and progression-free at 24 months since the start of treatment |
| Progression-free Survival (PFS) per Investigator Response Assessment | Up to 66 Months | PFS is defined as the time from the start of treatment to the first documentation of disease progression or death, whichever occurs first |
| Overall Survival (OS) | Up to 66 Months | OS is defined as the time from treatment initiation to death due to any cause |
| Number of Participants with Adverse Events (AEs) | From first dose of study drug to 30 days after last dose; up to 66 months for Arm A and Arm B | 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 |
Countries
Brazil, China, Italy, Poland, Spain, United States
Contacts
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed