Chronic Lymphocytic LeukemiaPhase 1/2NCT06697184
A Study to Investigate the Safety of Novel Dose Ramp-up Schedule(s) When Initiating Sonrotoclax in Participants Treated for Blood Cancers.
A Phase 1/2 study testing Sonrotoclax and Zanubrutinib in people with Chronic Lymphocytic Leukemia and CLL, run by BeOne Medicines at 20 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, CLL, Mantle Cell Lymphoma
- What is being tested?
- Sonrotoclax and Zanubrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 258 participants
- Where
- 20 sitesin 6 countries
- Study dates
- 23 Jan 2025to 30 Nov 2032
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stable Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- Adequate organ function and no very recent transfusion or blood growth factor
- 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):
- Confirmed diagnosis of CLL, based on Hallek et al 2018, and requiring treatment due to certain features of their disease
- At least 1 measurable lesion based on computed tomography (CT)/magnetic resonance imaging (MRI) and no history of prolymphocytic leukemia or Richter's transformation.
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- Only for participants with Mantle cell lymphoma (MCL):
- 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).
- 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.
- 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.
Who cannot join
- Participants unable to comply with the requirements of the protocol
- Serologic status reflecting active viral hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Positive HIV serology (HIVAb) status unless certain conditions are met.
- Participants with any major surgical procedure ≤ 28 days before first dose of study treatment
- Prior systemic treatment for the CLL
- Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment
- Prior exposure to a BCL-2 inhibitor
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
20 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
Study Director contact
20 sites in 6 countries
United States6 sites, 6 recruiting
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215-5418
- Recruiting
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, 46804
- Recruiting
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-4433
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110-1010
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612-9496
- Recruiting
The University of Kansas Cancer Center
Westwood, Kansas, 66205-2003
Australia6 sites, 6 recruiting
- Recruiting
Genesiscare St Andrews
Adelaide, South Australia, SA 5000
- Recruiting
Blacktown Cancer and Haematology Centre
Blacktown, New South Wales, NSW 2148
- Recruiting
Rockingham Hospital
Cooloongup, Western Australia, WA 6168
- Recruiting
Cabrini Hospital Malvern
Malvern, Victoria, VIC 3144
- Recruiting
The Alfred Hospital
Melbourne, Victoria, VIC 3004
- Recruiting
Linear Clinical Research
Nedlands, Western Australia, WA 6009
France3 sites, 3 recruiting
- Recruiting
Chu Dijon
Dijon, 21000
- Recruiting
Chu Montpellier Hopital Saint Eloi
Montpellier, 34090
- Recruiting
Iuct Oncopole
Toulouse, 31100
Brazil2 sites, 2 recruiting
- Recruiting
Hcfmusp Pesquisa Clinica Do Servico de Hematologia E Terapia Celular
São Paulo, 05403-010
- Recruiting
Hospital Santa Rita de Cassia Afecc
Vitória, 29043-260
United Kingdom2 sites, 2 recruiting
- Recruiting
Queen Elizabeth Hospital
Birmingham, B15 2TH
- Recruiting
St Jamess University Hospital
Leeds, LS9 7TF
China1 site, 1 recruiting
- Recruiting
Peking University Third Hospital
Beijing, Beijing Municipality, 100000
About this study
Official title: A Phase 1/2 Open-label Study to Investigate the Safety of Sonrotoclax Ramp-up Schedule(s) in Adult Patients With Hematological Malignancies.
The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.
Read the 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.
- Conditions
- Chronic Lymphocytic Leukemia, CLL, Mantle Cell Lymphoma, MCL
- Being tested
- Sonrotoclax, Zanubrutinib
- Keywords
- CLL previously untreated, Hematological Malignancies
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonrotoclaxDrug
Also called BGB-11417
Administered orally
ZanubrutinibDrug
Also called BGB-3111
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Arms: 1A,1B and 2A: Zanubrutinib + Sonrotoclax for TN CLL | Experimental | Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol. The total treatment duration is of 15 cycles of 28 days (including the phase of sonrotoclax dose ramp-up) Receives: Drug: Sonrotoclax; Drug: Zanubrutinib |
| Arms: 1C and 2B: Zanubrutinib + Sonrotoclax for R/R MCL | Experimental | Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol, for a total of 27 cycles of 28 days (including the phase of sonrotoclax ramp-up), then will continue on zanubrutinib alone until progression of their disease or other treatment discontinuation criteria. Receives: Drug: Sonrotoclax; Drug: Zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants who Experience Tumor Lysis Syndrome (TLS)
TLS will be defined by Howard criteria during the schedule-limiting toxicity (SLT) evaluation window
Measured: Up to approximately 4 months
Secondary outcomes (2)
Number of Participants with Adverse Events (AEs)
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 tolerability as determined by protocol-defined Cs during the SLT evaluation window
Measured: Up to approximately 4 months
Number of Participants with Dose Modifications During the SLT Evaluation Window
Measured: Up to approximately 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2024
- Study start23 Jan 2025
- Primary completion30 Nov 2029 (estimated)
- Study completion30 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by BeOne MedicinesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 258 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BeOne Medicines
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeOne Medicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06697184
- Sponsor's protocol ID
- BGB-11417-108
- Other IDs
- 2024-518829-15-00
- Status last verified
- Sep 2026
- First submitted
- 18 Nov 2024
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.