A Study to Investigate Sonrotoclax Combined With Zanubrutinib Versus Zanubrutinib Alone in Participants With Previously Untreated Chronic Lymphocytic Leukemia

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).
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Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
87
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.
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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

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A: Combination Therapy: Sonrotoclax + ZanubrutinibZanubrutinibParticipants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles.
Arm B: Monotherapy: ZanubrutinibZanubrutinibParticipants will receive zanubrutinib monotherapy daily until disease progression or unacceptable toxicity, whichever occurs first.
Arm A: Combination Therapy: Sonrotoclax + ZanubrutinibSonrotoclaxParticipants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles.
Primary Outcome Measures
NameTimeMethod
Complete Response (CR)/ Complete Response with Incomplete Bone Marrow Recovery (CRi) RateMonth 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
NameTimeMethod
Landmark Duration of Response Event-free Rate at 12 Months66 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) RateMonth 16

uMRD4 rate measured in both peripheral blood and bone marrow aspirate

CR/CRi Rate per Investigator Response AssessmentMonth 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 AssessmentUp 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 AssessmentUp 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 AssessmentUp 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 Assessment24 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 AssessmentUp 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 (32)

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

The First Affiliated Hospital, Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

University of Miami

🇺🇸

Miami, Florida, United States

Cleveland Clinic Florida

🇺🇸

Weston, Florida, United States

Northwest Georgia Oncology Centers Marietta

🇺🇸

Marietta, Georgia, United States

University of Maryland Greenebaum Comprehensive Cancer Center

🇺🇸

Baltimore, Maryland, United States

Nebraska Cancer Specialists (Satellite Site)

🇺🇸

Grand Island, Nebraska, United States

Nebraska Cancer Specialists

🇺🇸

Grand Island, Nebraska, United States

Instituto Dor de Pesquisa E Ensino Sao Paulo

🇧🇷

Sao Paulo, Brazil

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Summit Medical Group

🇺🇸

Florham Park, New Jersey, United States

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

🇧🇷

Sao Paulo, Brazil

Utah Cancer Specialists

🇺🇸

Sandy, Utah, United States

Centro de Pesquisas Oncologicas Cepon

🇧🇷

Florianopolis, Brazil

Hospital de Clinicas de Porto Alegre

🇧🇷

Porto Alegre, Brazil

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, Shanghai, 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

Pratia Onkologia Katowice

🇵🇱

Katowice, Poland

Pratia McM Krakow

🇵🇱

Krakow, Poland

Uniwersytecki Szpital Kliniczny Nr W Lublinie

🇵🇱

Lublin, Poland

Uniwersytecki Szpital Kliniczny Hematology

🇵🇱

Wroclaw, Poland

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hospital de Cabuenes

🇪🇸

Gijon, Spain

Clinica Universidad de Navarra

🇪🇸

Madrid, Spain

Start Madrid Fundacion Jimenez Diaz

🇪🇸

Madrid, Spain

Clinica Universidad de Navarra Pamplona

🇪🇸

Pamplona, Spain

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