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

ConditionCLL / SLL
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorYi Shuhua

About this trial

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.

Eligibility criteria

Qualifiers

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).

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.

Disqualifiers

1. 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.

Trial design

Treatments tested in this trial

  • 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax
  • zanubrutinib maintenance until disease progression

Treatment groups

60 Participants
are divided into 2 treatment groups

Locations

7
Shenzhen Second People's Hospital ShenzhenGuangdong, China
Henan Cancer Hospital ZhengzhouHenan, China
The Second Xiangya Hospital of Central South University ChangshaHunan, China
Jiangsu Province Hospital NanjingJiangsu, China

Sponsors and collaborators

Yi Shuhua

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Sponsor institution

BeOne Medicines

Collaborator