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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

This trial does not accept healthy volunteers

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

Design model

Parallel

Treatments tested in this trial

  • 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)

  • zanubrutinib maintenance until disease progression

    Drug

    Continuous zanubrutinib monotherapy until disease progression or intolerable toxicity occurs.

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Low-risk group（Without del17p and/or TP53 mutation）Experimental treatment 1 intervention
Group B: High-risk group(With del17p and/or TP53 mutation)Experimental treatment 2 interventions

Trial outcomes

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)

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

Secondary outcomes

1

Objective Response Rate

The proportion of patients who achieve a Complete Response (CR) and a Partial Response (PR) according to standardized criteria

Time frame
At the end of 12 cycles (each cycle is 28 days) of combination therapy
2

Complete Response Rate

The percentage of patients who meet the stringent criteria for Complete Remission

Time frame
At the end of 12 cycles (each cycle is 28 days) of combination therapy
3

Duration of Response

The time from the first documented objective response (CR or PR) until disease progression (PD) or death from any cause.

Time frame
up to 8 years
4

Progression-Free Survival

The time from treatment initiation (or randomization) to disease progression or death

Time frame
up to 8 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Yi Shuhua

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Sponsor institution

BeOne Medicines

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: