CLL (Chronic Lymphocytic Leukemia)Phase 2NCT07671378
A Study of MRD-Guided Zanubrutinib Plus Sonrotoclax in Treatment-Naïve, High-Risk CLL/SLL Patients
A Phase 2 study testing Zanubrutinib and sonrotoclax in people with CLL (Chronic Lymphocytic Leukemia), run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This study is a prospective, multicenter, open-label, single-arm phase II clinical trial evaluating the efficacy and safety of an MRD-guided, time-limited therapy with zanubrutinib combined with sonrotoclax in previously untreated high-risk CLL/SLL patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- CLL (Chronic Lymphocytic Leukemia)
- What is being tested?
- Zanubrutinib and sonrotoclax
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2026to 31 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following inclusion criteria to be enrolled in this study:
- Age between 18 and 75 years, inclusive. Diagnosis of CLL/SLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria.
- Meeting iwCLL 2018 treatment indications and carrying at least one high-risk factor, including CLL-IPI high-risk/very high-risk, del(11q), del(17p)/TP53 mutation, unmutated IGHV, or complex karyotype.
- Measurable disease: presence of measurable lymphadenopathy by computed tomography (CT) scan.
- ECOG performance status of 0 to 2.
- Adequate major organ function meeting the following criteria:
Show all 13Show fewer
- Hematologic function: without transfusion or hematopoietic growth factor support for at least 7 days prior to enrollment (at least 14 days for pegylated G-CSF such as pegfilgrastim), and meeting the following criteria: absolute neutrophil count (ANC) > 0.75 × 10⁹/L, platelet count (PLT) > 30 × 10⁹/L, hemoglobin (Hb) > 80 g/L.
- Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN).
- Creatinine clearance (CrCl) ≥ 60 mL/min (estimated by Cockcroft-Gault formula).
- Total bilirubin (TBIL) ≤ 1.5 × ULN (unless due to Gilbert's syndrome or other non-hepatic causes).
- Coagulation function: prothrombin time (PT)/international normalized ratio (INR) < 1.5 × ULN, activated partial thromboplastin time (APTT) < 1.5 × ULN (exceptions may be considered on a case-by-case basis if clearly unrelated to coagulopathy or bleeding disorders).
- Life expectancy ≥ 6 months. Female subjects of non-childbearing potential (e.g., postmenopausal for ≥ 1 year with amenorrhea, history of hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) are eligible. Female subjects of childbearing potential must have a negative serum pregnancy test at enrollment.
- Able to understand and voluntarily sign a written informed consent form.
Who cannot join
- Patients meeting any of the following criteria will be excluded from this study:
- Any prior treatment for CLL or SLL (including but not limited to chemotherapy, targeted therapy, immunomodulatory therapy, radiotherapy, and/or monoclonal antibody therapy).
- History of other malignancies, unless:
- The malignancy has been cured with no known active disease for at least 3 years prior to the first dose and is considered by the treating physician to carry a low risk of recurrence.
- Adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease.
- Adequately treated carcinoma in situ with no evidence of disease. Known or suspected history of Richter's transformation. Uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia. Subjects with a decline in hemoglobin level or platelet count due to autoimmune destruction within 4 weeks prior to first dose, or requiring > 20 mg prednisone daily (or equivalent) to treat or control autoimmune disease.
Show all 18Show fewer
- Use of > 20 mg/day prednisone within 7 days prior to first dose of study drug (unless used for prophylaxis or treatment of allergic reactions, such as to contrast media).
- Known allergic reaction to any of the study drugs. Known hypersensitivity to xanthine oxidase inhibitors and/or rasburicase. Subjects with hypersensitivity to xanthine oxidase inhibitors who cannot receive rasburicase will be excluded.
- Receipt of a live attenuated vaccine within 4 weeks prior to first dose of study drug.
- Active infection requiring systemic therapy that is ongoing or completed within 14 days prior to first dose, or any uncontrolled active systemic infection.
- Known bleeding disorders (e.g., von Willebrand disease or hemophilia). History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Known history of HIV infection, or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subjects who are positive for HBV core antibody, hepatitis B surface antigen (HBsAg), or HCV antibody must have a negative PCR result prior to enrollment. Subjects with a positive PCR result will be excluded.
- Major surgery within 4 weeks prior to first dose. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's judgment, could compromise the subject's safety or pose an undue risk to the study results.
- Current active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia, New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, or history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months.
- Inability to swallow capsules/tablets, or presence of malabsorption syndrome, disease significantly affecting gastrointestinal function, history of partial or total gastrectomy or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- Concurrent use of warfarin or other vitamin K antagonists. Requirement for treatment with strong cytochrome P450 (CYP) 3A inhibitors. Current active, clinically significant hepatic impairment meeting Child-Pugh Class B or C criteria.
- Female subjects who are lactating or pregnant. Unwilling or unable to participate in all required study assessments and procedures.
- Inability to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization for use of protected health information (in accordance with national and local privacy regulations).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Jiangsu Province Hospital
Nanjing, Jiangsu, 210000
Huayuan Zhu, MD,PhD, +86-13813810650, huayuan.zhu@hotmail.com
Huayuan Zhu, MD
About this study
Official title: A Prospective Study of MRD-Guided, Time-Limited Therapy With Zanubrutinib Plus Sonrotoclax in Treatment-Naïve, High-Risk Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Patients
This study is a prospective, multicenter, open-label, single-arm phase II clinical trial evaluating the efficacy and safety of an MRD-guided, time-limited therapy with zanubrutinib combined with sonrotoclax in previously untreated high-risk CLL/SLL patients.
- Conditions
- CLL (Chronic Lymphocytic Leukemia)
- Being tested
- Zanubrutinib and sonrotoclax
- Keywords
- BCL2i, MRD
- Medical subject headings
- Leukemia, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zanubrutinib and sonrotoclaxDrug
Zanubrutinib: 160 mg BID, orally, administered until Cycle 15, 21, or 27, and thereafter until discontinuation criteria are met, disease progression, or unacceptable toxicity.(28d/cycle) Sonrotoclax: Starting from Day 1 of Cycle 3, a 4-week dose-escalation regimen is administered until the target dose of 320 mg QD is reached, then administered orally until Cycle 15, 21, or 27, and thereafter until discontinuation criteria are met, disease progression, or unacceptable toxicity. All patients must complete at least 12 cycles of combination therapy with zanubrutinib and sonrotoclax (C4-C15), with a maximum of 24 cycles of combination therapy (C4-C27). If uMRD6 is not achieved after 24 cycles of combination therapy, patients will receive zanubrutinib monotherapy as maintenance. For patients in whom assessment is feasible, treatment discontinuation may be considered upon achieving uMRD6 at any time point. Otherwise, treatment will be continued until disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Zanubrutinib+Sonrotoclax | Experimental | Zanubrutinib+Sonrotoclax for Pathologically confirmed, treatment-naïve CLL/SLL patients who meet the criteria for treatment initiation and carry at least one high-risk feature. Receives: Drug: Zanubrutinib and sonrotoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
uMRD6 rate at Cycle 15
defined as the proportion of patients achieving undetectable minimal residual disease (MRD negativity, <10-⁶) in peripheral blood as assessed by next-generation sequencing (NGS)
Measured: At the end of Cycle 15 (each cycle is 28 days)
Secondary outcomes (5)
complete response (CR) rate
Overall response rate is the proportion of patients who achieve a complete response to treatment defined by the iwCLL.
Measured: On Day 1 of Cycle 7, Day 1 of Cycle 19, Day 1 of Cycle 13, Day 1 of Cycle 16, Day 1 of Cycle 19, End of Treatment (each cycle is 28 days)
3-year Progression-free survival rate
PFS is defined as the time from the first dose of treatment to progression, or death due to any cause, whichever occurs first. For subjects without progression, relapse, or death at the time of analysis, EFS will be censored at the last assessment date.
Measured: From the first dose of treatment until the date of progression or date of death from any cause, whichever came first.assessed up to 3 years ( 36 month) .
3-year Overall survival tare
OS is defined as the time from the first dose of treatment to death due to any cause. Subjects who remain alive at the time of analysis will be censored at the last known alive date of the subject.
Measured: lFrom the first dose of treatment until the date of death from any cause, whichever came first.assessed up to 3 years( 36 month) .
uMRD4 and uMRD6 rates of EOT
uMRD4 and uMRD6 rates assessed by flow cytometry and NGS after the actual end of combination therapy.
Measured: On Day 1 of Cycle 16, Day 1 of Cycle 19, Day 1 of Cycle 22, Day 1 of Cycle 25 (up to 25 cycles, each cycle is 28 days).
Number of participants with any adverse events (Safety assessed by NCI-CTC AE v5.0)
All treatment-emergent AEs will be included in the analysis. For each AE, the number and percentage of subjects who experience at least one occurrence of the given event will be summarized. The number and percent of subjects with TEAEs will be summarized according to intensity (CTCAE, v5) for hematologic toxicity, and drug relationship, as well as categorized by system organ class and preferred term. Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those subjects who die, who discontinue treatment due to an AE, or who experience a severe AE or a SAE.
Measured: Safety was evaluated everyday during induction and maintenance therapy. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2026
- Study start1 Jun 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CLL (Chronic Lymphocytic Leukemia)Studies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07671378
- Sponsor's protocol ID
- 2026-SR-398
- Status last verified
- Jun 2026
- First submitted
- 9 Jun 2026
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of MRD-Guided, Time-Limited Therapy With Zanubrutinib Plus Sonrotoclax in Treatment-Naïve, High-Risk Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Patients
- ClinicalTrials.gov ID
- NCT07671378
- Acronym / sponsor ID
- 2026-SR-398
- Conditions
- CLL (Chronic Lymphocytic Leukemia)
- Keywords
- BCL2i, MRD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 26 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a prospective, multicenter, open-label, single-arm phase II clinical trial evaluating the efficacy and safety of an MRD-guided, time-limited therapy with zanubrutinib combined with sonrotoclax in previously untreated high-risk CLL/SLL patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zanubrutinib+Sonrotoclax | Experimental | Drug: Zanubrutinib and sonrotoclaxZanubrutinib+Sonrotoclax for Pathologically confirmed, treatment-naïve CLL/SLL patients who meet the criteria for treatment initiation and carry at least one high-risk feature. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must meet all of the following inclusion criteria to be enrolled in this study:
- Age between 18 and 75 years, inclusive. Diagnosis of CLL/SLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria.
- Meeting iwCLL 2018 treatment indications and carrying at least one high-risk factor, including CLL-IPI high-risk/very high-risk, del(11q), del(17p)/TP53 mutation, unmutated IGHV, or complex karyotype.
- Measurable disease: presence of measurable lymphadenopathy by computed tomography (CT) scan.
- ECOG performance status of 0 to 2.
Key exclusion criteria (18 listed)
- Patients meeting any of the following criteria will be excluded from this study:
- Any prior treatment for CLL or SLL (including but not limited to chemotherapy, targeted therapy, immunomodulatory therapy, radiotherapy, and/or monoclonal antibody therapy).
- The malignancy has been cured with no known active disease for at least 3 years prior to the first dose and is considered by the treating physician to carry a low risk of recurrence.
- Adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease.
- Adequately treated carcinoma in situ with no evidence of disease. Known or suspected history of Richter's transformation. Uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia. Subjects with a decline in hemoglobin level or platelet count due to autoimmune destruction within 4 weeks prior to first dose, or requiring > 20 mg prednisone daily (or equivalent) to treat or control autoimmune disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zanubrutinib and sonrotoclaxZanubrutinib: 160 mg BID, orally, administered until Cycle 15, 21, or 27, and thereafter until discontinuation criteria are met, disease progression, or unacceptable toxicity.(28d/cycle) Sonrotoclax: Starting from Day 1 of Cycle 3, a 4-week dose-escalation regimen is administered until the target dose of 320 mg QD is reached, then administered orally until Cycle 15, 21, or 27, and thereafter until discontinuation criteria are met, disease progression, or unacceptable toxicity. All patients must complete at least 12 cycles of combination therapy with zanubrutinib and sonrotoclax (C4-C15), with a maximum of 24 cycles of combination therapy (C4-C27). If uMRD6 is not achieved after 24 cycles of combination therapy, patients will receive zanubrutinib monotherapy as maintenance. For patients in whom assessment is feasible, treatment discontinuation may be considered upon achieving uMRD6 at any time point. Otherwise, treatment will be continued until disease progression. | Drug | Zanubrutinib+Sonrotoclax |
Primary outcome
uMRD6 rate at Cycle 15
Time frame: At the end of Cycle 15 (each cycle is 28 days)
defined as the proportion of patients achieving undetectable minimal residual disease (MRD negativity, <10-⁶) in peripheral blood as assessed by next-generation sequencing (NGS)
5 secondary outcomes
complete response (CR) rate
Time frame: On Day 1 of Cycle 7, Day 1 of Cycle 19, Day 1 of Cycle 13, Day 1 of Cycle 16, Day 1 of Cycle 19, End of Treatment (each cycle is 28 days)
3-year Progression-free survival rate
Time frame: From the first dose of treatment until the date of progression or date of death from any cause, whichever came first.assessed up to 3 years ( 36 month) .
3-year Overall survival tare
Time frame: lFrom the first dose of treatment until the date of death from any cause, whichever came first.assessed up to 3 years( 36 month) .
uMRD4 and uMRD6 rates of EOT
Time frame: On Day 1 of Cycle 16, Day 1 of Cycle 19, Day 1 of Cycle 22, Day 1 of Cycle 25 (up to 25 cycles, each cycle is 28 days).
Number of participants with any adverse events (Safety assessed by NCI-CTC AE v5.0)
Time frame: Safety was evaluated everyday during induction and maintenance therapy. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for CLL (Chronic Lymphocytic Leukemia)
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanubrutinib and sonrotoclax in people with CLL (Chronic Lymphocytic Leukemia), run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Huayuan ZHU, MD, phD (+86-13813810650, huayuan.zhu@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
uMRD6 rate at Cycle 15 (time frame: At the end of Cycle 15 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2026.