A Phase 1/2 Open-label Study to Investigate the Safety of Sonrotoclax Ramp-up Schedule(s) in Adult Patients With Hematological Malignancies.
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.
Arms & interventions
- DrugSonrotoclax
Administered orally
- DrugZanubrutinib
Administered orally
Outcome measures
Primary
Number of Participants who Experience Tumor Lysis Syndrome (TLS)
TLS will be defined by Howard criteria during the schedule-limiting toxicity (SLT) evaluation window
Time frame: Up to approximately 4 months
Secondary
Number of Participants with Adverse Events (AEs)
Time frame: Up to approximately 4 months
Number of Participants with Dose Modifications During the SLT Evaluation Window
Time frame: Up to approximately 4 months
Eligibility criteria
Study locations (6)
Moffitt Cancer Center
Tampa, Florida, 33612-9496
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, 46804
The University of Kansas Cancer Center
Westwood, Kansas, 66205-2003
Dana Farber Cancer Institute
Boston, Massachusetts, 02215-5418
Washington University School of Medicine
St Louis, Missouri, 63110-1010
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-4433