Clinical trial NCT06637501: A Study to Investigate Sonrotoclax Combined With Zanubrutinib Versus Zanubrutinib Alone in Participants With Previously Untreated Chronic Lymphocytic Leukemia
Official title: A Multicenter, Open-Label, Phase 2 Study to Investigate the Efficacy and Safety of Sonrotoclax Combined With Zanubrutinib Compared With Zanubrutinib Monotherapy in Adult Patients With Previously Untreated Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: CLL
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-10-15
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 CT/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 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/Exclusion criteria may apply

Primary outcomes:
measure: Complete Response (CR)/ Complete Response with Incomplete Bone Marrow Recovery (CRi) Rate
timeFrame: Month 16
Secondary outcomes:
measure: Undetectable Minimal Residual Disease at < 10^-4Sensitivity (uMRD4) Rate
timeFrame: Month 16
measure: CR/CRi Rate per Investigator Response Assessment
timeFrame: Month 16
measure: Overall Response Rate (ORR) per IRC and Investigator Response Assessment
timeFrame: Up to 66 Months
measure: Landmark Duration of Response Event-free Rate at 12 Months
timeFrame: 66 months
measure: Duration of Response (DOR) per Investigator Response Assessment
timeFrame: Up to 66 Months
measure: Time to Response (TTR) per IRC and Investigator Response Assessment
timeFrame: Up to 66 Months
measure: Landmark Progression-free Survival Rate at 24 Months per Investigator Assessment
timeFrame: 24 Months
measure: Progression-free Survival (PFS) per Investigator Response Assessment
timeFrame: Up to 66 Months
measure: Overall Survival (OS)
timeFrame: Up to 66 Months
measure: Number of Participants with Adverse Events (AEs)
timeFrame: From first dose of study drug to 30 days after last dose; up to 66 months for Arm A and Arm B
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers Marietta
state: Georgia
city: Niles
country: United States
facility: Illinois Cancer Specialists (Niles) Usor
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Omaha
country: United States
facility: Nebraska Cancer Specialists (Satellite Site)
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Shirley
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Eugene
country: United States
facility: Oncology Associates of Oregon Willamette Valley Cancer Center
state: Oregon
city: Dallas
country: United States
facility: Texas Oncology Dfw
state: Texas
city: Tyler
country: United States
facility: Texas Oncology Tyler
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Vancouver
country: United States
facility: Northwest Cancer Specialist, Pc(Us Oncology Research)
state: Washington
city: Florianopolis
country: Brazil
facility: Centro de Pesquisas Oncologicas Cepon
city: Porto AlegreRS
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Sao Paulo
country: Brazil
facility: Instituto Dor de Pesquisa E Ensino Sao Paulo
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changzhou
country: China
facility: The First Peoples Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
city: Firenze
country: Italy
facility: Aou Careggi, Servizio Sanitario Toscana
city: Modena
country: Italy
facility: Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
city: Palermo
country: Italy
facility: Aoor Villa Sofia Cervello
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Krakow
country: Poland
facility: Pratia McM Krakow
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr W Lublinie
city: Wrocaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny Hematology
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Gijon
country: Spain
facility: Hospital de Cabuenes
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra Pamplona
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: