Zanubrutinib Induction Followed by Delayed Fixed-Duration Combination With Sonrotoclax for CLL/SLL：Stop Trial 2.0

NCT07682415 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT2026068
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief Summary

The goal of this clinical trial is to learn if zanubrutinib induction followed by delayed fixed-duration combination with sonrotoclax works to treat previously untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL). It will also learn about the safety of this combination regimen. The main questions it aims to answer are:Does this combination therapy achieve undetectable minimal residual disease (uMRD) in participants?What medical problems (adverse events) do participants have when taking zanubrutinib and sonrotoclax?Researchers will conduct a single-arm study to systematically evaluate the MRD clearance, efficacy, safety, and immune-related functions of this specific treatment sequence.Participants will:Low-risk group (without 17p deletion/TP53 mutation): Take zanubrutinib monotherapy for 12 cycles, followed by combination zanubrutinib + sonrotoclax for 12 cycles, then discontinue treatment for observation.High-risk group (with 17p deletion/TP53 mutation): Follow the same initial regimen (12 cycles monotherapy + 12 cycles combination), followed by zanubrutinib monotherapy maintenance until disease progression.Visit the clinic periodically for MRD assessment (via flow cytometry), efficacy evaluation (CT/PET-CT, lab tests), and safety checks (physical exam, blood tests, ECG).Undergo immune function evaluation via peripheral blood samples to assess changes in T-cell counts and subsets.

Conditions

CLL / SLL

Keywords

Zanubrutinib; Sonrotoclax; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• uMRD rate

  Proportion of patients achieving undetectable minimal residual disease (uMRD, defined as MRD \<10-⁴, fewer than 1 CLL cell per 10,000 leukocytes)

  At the end of 12 cycles (each cycle is 28 days) of combination therapy

Secondary Outcomes (5)

• Objective Response Rate

  At the end of 12 cycles (each cycle is 28 days) of combination therapy

• Complete Response Rate

  At the end of 12 cycles (each cycle is 28 days) of combination therapy

• Duration of Response

  up to 8 years

• Progression-Free Survival

  up to 8 years

• Overall Survival

  up to 8 years

Study Arms (2)

Low-risk group（Without del17p and/or TP53 mutation）

EXPERIMENTAL

12 cycles of zanubrutinib monotherapy induction → 12 cycles of zanubrutinib combined with sonrotoclax → discontinuation of study drugs followed by regular follow-up

Drug: 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax

High-risk group(With del17p and/or TP53 mutation)

EXPERIMENTAL

12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax, then zanubrutinib maintenance monotherapy until disease progression or intolerable toxicity occurs.

Drug: 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax; Drug: zanubrutinib maintenance until disease progression

Interventions

12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax DRUG

12 cycles of zanubrutinib monotherapy induction → 12 cycles of zanubrutinib combined with sonrotoclax → discontinuation of study drugs followed by regular follow-up Zanubrutinib Dosage The total daily oral dose is 320 mg. The dosing schedule is 160 mg (2 × 80 mg capsules) twice daily, Sonrotoclax Dose Escalation Schedule Cycle 13 Week 1 (C13W1): Days 1-3: 1 mg daily (1 × 1 mg tablet); Days 4-7: 2 mg daily (2 × 1 mg tablets) Cycle 13 Week 2 (C13W2): Days 1-3: 5 mg daily (1 × 5 mg tablet); Days 4-7: 10 mg daily (2 × 5 mg tablets) Cycle 13 Week 3 (C13W3): Days 1-3: 20 mg daily (1 × 20 mg tablet); Days 4-7: 40 mg daily (2 × 20 mg tablets) Cycle 13 Week 4 (C13W4): Days 1-3: 80 mg daily (1 × 80 mg tablet); Days 4-7: 160 mg daily (2 × 80 mg tablets) Cycle 14 Week 1 (C14W1) and all subsequent cycles: 320 mg daily (4 × 80 mg tablets)

High-risk group(With del17p and/or TP53 mutation); Low-risk group（Without del17p and/or TP53 mutation）

zanubrutinib maintenance until disease progression DRUG

Continuous zanubrutinib monotherapy until disease progression or intolerable toxicity occurs.

High-risk group(With del17p and/or TP53 mutation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years, no restriction on gender.
• Newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) consistent with the Chinese Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (2025 Edition).
• Meet at least one of the following indications for CLL treatment:
• Evidence of progressive bone marrow failure manifested by progressive reduction in hemoglobin and/or platelet counts.
• Massive splenomegaly (spleen palpable \>6 cm below the left costal margin) or symptomatic splenomegaly.
• Bulky lymphadenopathy (maximum diameter \>10 cm) or symptomatic lymphadenopathy.
• Progressive lymphocytosis: ≥50% increase in lymphocyte count within 2 months, or lymphocyte doubling time (LDT) \<6 months. LDT alone shall not serve as an indication for treatment if the baseline lymphocyte count is \<30×10⁹/L.
• Symptomatic organ dysfunction caused by CLL/SLL (involving skin, kidney, lung, spine and other organs).
• Autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) with inadequate response to corticosteroid therapy.
• At least one of the following disease-related B symptoms:
• Unintentional weight loss ≥10% within the preceding 6 months without identifiable cause; ② Severe fatigue (ECOG performance status ≥2, inability to perform routine daily activities);
• ③ Unexplained fever \>38.0 °C lasting ≥2 weeks without confirmed infection;
• ④ Unexplained night sweats persisting for more than 1 month without confirmed infection.
• ECOG performance status ≤2.
• Major organ function meets the following criteria within 7 days prior to treatment initiation:

You may not qualify if:

• \. Previously received any systemic anti-tumor therapy for CLL/SLL. 2. Pathologically confirmed transformation to Richter's syndrome via biopsy. 3. Severe non-lymphoma-related hepatic or renal impairment defined as: ALT/AST \>3×ULN or TBIL \>2×ULN; creatinine clearance \<30 mL/min or serum creatinine \>2×ULN.
• \. Significant pre-existing renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular or hepatic disease judged by the investigator to compromise trial participation.
• \. Other uncontrolled clinically significant medical conditions including but not limited to:
• a. Uncontrolled systemic infection (viral, bacterial, fungal); positive hepatitis B surface antigen with HBV-DNA \>1000 IU/mL; positive anti-HCV antibody or detectable HCV-RNA; positive anti-HIV antibody.
• b. Active uncontrolled autoimmune diseases other than autoimmune cytopenias. 6. Clinical signs of central nervous system (CNS) dysfunction or documented CNS infiltration by disease.
• \. Received major surgery (excluding lymph node biopsy) within 14 days prior to enrollment or scheduled to undergo major surgery during trial treatment.
• \. Inability to swallow capsules, malabsorption syndrome, or severe gastrointestinal disorders including prior gastrectomy, small bowel resection, symptomatic inflammatory bowel disease, ulcerative colitis, partial or complete intestinal obstruction.
• \. Concurrent use of strong CYP3A inhibitors or inducers during study drug initiation and dose titration period.
• \. Pregnant or breastfeeding females; females of childbearing potential without reliable contraceptive measures.
• \. Clinically significant cardiovascular disease (NYHA cardiac functional class III/IV); history of myocardial infarction, malignant arrhythmia (including QTc ≥480 ms), inadequately controlled hypertension (systolic BP ≥150 mmHg, diastolic BP ≥100 mmHg) or unstable angina within 6 months before enrollment.
• \. History of severe hypersensitivity to any active ingredient or excipient of the investigational product.
• \. Systemic disorders that may impair patient compliance with trial requirements.

Sponsors & Collaborators

• Yi Shuhua: lead
• BeOne Medicines: collaborator

Study Sites (7)

Shenzhen Second People's Hospital

Shenzhen, Guangdong, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Location

Qilu Hospital of Shandong University

Jinan, Shandong, China

Location

Blood Disease Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, CAMS)

Tianjin, Tianjin Municipality, 300000, China

Location

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MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shuhua Yi, Docter

  Blood Disease Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, CAMS)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuhua Yi, Doctor

CONTACT

（+86）15900265415; yishuhua@ihcams.ac.cn

Tingyu Wang, Doctor

CONTACT

wangtingyu@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: July 2, 2026
• Study Start: June 8, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): August 1, 2034
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: June 2026-January 2030
• Access Criteria: Researchers who are interested in the study can obtain the above information by sending an email to my mailbox

Locations

CN (7)