A Study to Investigate Sonrotoclax Combined With Zanubrutinib Versus Zanubrutinib Alone in Participants With Previously Untreated Chronic Lymphocytic Leukemia
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT06637501
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study is to support the registration plan of sonrotoclax plus zanubrutinib treatment in participants with previously untreated 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 87
- Previously untreated adult patient ≥ 18 years with a confirmed diagnosis of CLL.
- CLL requiring treatment as per pre-defined criteria.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2.
- Measurable disease by CT/MRI.
- Adequate marrow function.
- Adequate liver function as indicated by aspartate aminotransferase (AST) alanine aminotransferase (ALT) and serum total bilirubin.
- Adequate renal function.
- Life expectancy > 6 months.
- Signed informed consent and able to comply with the study protocol in the investigator's judgment.
- 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.
- Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
- Known central nervous system involvement
- Received previous systemic treatment for CLL
- Clinically significant cardiovascular disease
- Severe or debilitating pulmonary disease
- History of prior malignancy
- Active fungal, bacterial, and/or viral infection requiring systemic therapy
- Positive HIV serology (HIVAb) status or serologic status reflecting active hepatitis B or C infection
- Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment
- 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
- History of stroke or intracranial hemorrhage ≤ 6 months before the first dose of study treatment
- Unable to swallow capsules or tablets or diseases significantly affecting GI function
- Hypersensitivity to zanubrutinib, sonrotoclax, or any of its excipients
- Use of investigational agents within the last 4 weeks before screening
- Pregnant and lactating females
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Combination Therapy: Sonrotoclax + Zanubrutinib Zanubrutinib Participants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles. Arm B: Monotherapy: Zanubrutinib Zanubrutinib Participants will receive zanubrutinib monotherapy daily until disease progression or unacceptable toxicity, whichever occurs first. Arm A: Combination Therapy: Sonrotoclax + Zanubrutinib Sonrotoclax Participants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Landmark Duration of Response Event-free Rate at 12 Months 66 months The 12-month landmark duration of response event-free rate is defined as the proportion of responders who remain alive and progression-free at 12 months since the first determination of response.
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 proportion 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 proportion 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 the first determination of response until first documentation of progression or death, whichever occurs first
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 proportion 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 and the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) grading scale for hematologic toxicities in CLL Studies as appropriate.
Trial Locations
- Locations (38)
Pratia McM Krakow
🇵🇱Krakow, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
University of Miami
🇺🇸Miami, Florida, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Northwest Georgia Oncology Centers Marietta
🇺🇸Marietta, Georgia, United States
Illinois Cancer Specialists (Niles) Usor
🇺🇸Niles, Illinois, United States
University of Maryland Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Nebraska Cancer Specialists (Satellite Site)
🇺🇸Omaha, Nebraska, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Summit Medical Group
🇺🇸Florham Park, New Jersey, United States
New York Cancer and Blood Specialists
🇺🇸Shirley, New York, United States
Oncology Associates of Oregon Willamette Valley Cancer Center
🇺🇸Eugene, Oregon, United States
Texas Oncology Dfw
🇺🇸Dallas, Texas, United States
Texas Oncology Tyler
🇺🇸Tyler, Texas, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Northwest Cancer Specialist, Pc(Us Oncology Research)
🇺🇸Vancouver, Washington, United States
Centro de Pesquisas Oncologicas Cepon
🇧🇷Florianopolis, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷Porto AlegreRS, Brazil
Instituto Dor de Pesquisa E Ensino Sao Paulo
🇧🇷Sao Paulo, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
🇧🇷Sao Paulo, Brazil
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The First Peoples Hospital of Changzhou
🇨🇳Changzhou, Jiangsu, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
🇮🇹Brescia, Italy
Aou Careggi, Servizio Sanitario Toscana
🇮🇹Firenze, Italy
Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
🇮🇹Modena, Italy
Aoor Villa Sofia Cervello
🇮🇹Palermo, Italy
Uniwersytecki Szpital Kliniczny Nr W Lublinie
🇵🇱Lublin, Poland
Uniwersytecki Szpital Kliniczny Hematology
🇵🇱Wrocaw, Poland
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de Cabuenes
🇪🇸Gijon, Spain
Clinica Universidad de Navarra
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Clinica Universidad de Navarra Pamplona
🇪🇸Pamplona, Spain