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NCT06697184PHASE1, PHASE2Recruiting

A Study to Investigate the Safety of Novel Dose Ramp-up Schedule(s) When Initiating Sonrotoclax in Participants Treated for Blood Cancers.

BeOne Medicines

Start Date

1/23/2025

Completion Date

11/30/2032

Summary

The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.

Detailed Description

This study will test the safety of novel sonrotoclax dosing with gradual increases of sonrotoclax dose over specified periods until the intended target daily dose is reached. The focus will be on tumor lysis syndrome (TLS) and related toxicity signals. Sonrotoclax is a drug that works by blocking a protein called B-cell lymphoma-2 (BCL-2). 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 certain malignant diseases including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The start of treatment with BCL-2 inhibitor requires a gradual ramp-up over the first weeks to avoid potential consequences of initial tumor cell breakage and the release of cell content in the bloodstream. Several ramp-up schedules have already been explored, and this study aims to optimize the dosing ramp-up schedule that may be beneficial to patients and caregivers. 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 and MCL. This study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 17 months for treatment-naïve (TN) CLL participants or approximately 32 months for relapsed/refractory (R/R) MCL participants.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Stable Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. 2. Adequate organ function and no very recent transfusion or blood growth factor 3. Participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 7 days after the last dose of sonrotoclax or 1 month after the last dose of zanubrutinib, whichever is later. Only for participants with Chronic Lymphocytic Leukemia (CLL): 4. Confirmed diagnosis of CLL, based on Hallek et al 2018, and requiring treatment due to certain features of their disease 5. At least 1 measurable lesion based on computed tomography (CT)/magnetic resonance imaging (MRI) and no history of prolymphocytic leukemia or Richter's transformation. Only for participants with Mantle cell lymphoma (MCL): 6. Historically confirmed diagnosis of MCL based on the World Health Organization 2022 classification of Haematolymphoid Tumors (WHO-HEAM5) or based on International Consensus Classification (ICC). 7. Relapsed or refractory to the last line of therapy and have received at least 1 prior line of systemic therapy. Note: A line of therapy is considered ≥ 2 consecutive cycles of a systemic anticancer regimen. Patients with prior BTKi therapy should not have progressed during treatment or relapsed within 12 months after BTKi discontinuation. 8. Measurable disease defined as ≥ 1 nodal lesion that is \> 1.5 cm in longest diameter, or ≥ 1 extranodal lesion that is \> 1 cm in longest diameter. Exclusion Criteria: 1. Participants unable to comply with the requirements of the protocol 2. Serologic status reflecting active viral hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 3. Positive HIV serology (HIVAb) status unless certain conditions are met. 4. Participants with any major surgical procedure ≤ 28 days before first dose of study treatment 5. Prior systemic treatment for the CLL 6. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment 7. Prior exposure to a BCL-2 inhibitor NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Interventions

DRUG

Sonrotoclax

DRUG

Zanubrutinib

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Conditions

Chronic Lymphocytic LeukemiaCLLMantle Cell LymphomaMCL

Locations

Moffitt Cancer Center

Tampa, Florida 33612-9496

United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana 46804

United States

The University of Kansas Cancer Center

Westwood, Kansas 66205-2003

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02215-5418

United States

Washington University School of Medicine

St Louis, Missouri 63110-1010

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington 98109-4433

United States

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales NSW 2148

Australia

Genesiscare St Andrews

Adelaide, South Australia SA 5000

Australia

Cabrini Hospital Malvern

Malvern, Victoria VIC 3144

Australia

The Alfred Hospital

Melbourne, Victoria VIC 3004

Australia

Rockingham Hospital

Cooloongup, Western Australia WA 6168

Australia

Linear Clinical Research

Nedlands, Western Australia WA 6009

Australia

Chu Dijon

Dijon, 21000

France

Chu Montpellier Hopital Saint Eloi

Montpellier, 34090

France

Iuct Oncopole

Toulouse, 31100

France

Queen Elizabeth Hospital

Birmingham, B15 2TH

United Kingdom

St Jamess University Hospital

Leeds, LS9 7TF

United Kingdom