RecruitingPhase 2NCT06958705

Venetoclax as Consolidation in CLL Patients Treated With BTK Inhibitor Monotherapy

Study of the Efficacy and Safety of Venetoclax as Consolidation to Achieve Fix-Duration Treatment in CLL Patients Treated With BTK Inhibitor Monotherapy


Sponsor

The First Affiliated Hospital with Nanjing Medical University

Enrollment

79 participants

Start Date

Dec 1, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This is an open-label, multicenter, phase 2, non-randomized study aiming to study the efficacy and safety of fixed-duration venetoclax consolidation in CLL patients who are on BTK inhibitor monotherapy. Patients who are on BTK inhibitor monotherapy for ≥ 6 months and still responsive are included. The study includes patients who are treatment-naive before taking BTK inhibitors. Patients will be treated with the BTK inhibitor plus full-dose venetoclax for 12 cycles after a standard 5-week dose ramp-up. Peripheral blood and bone marrow MRD status will be evaluated during and after the treatment. After the completion of combination therapy, patients will stop both BTK inhibitor and venetoclax and be followed.


Eligibility

Min Age: 18 YearsMax Age: 80 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether adding venetoclax — a targeted cancer drug — as a consolidation treatment (an extra treatment after initial response) can help clear remaining cancer cells in people with chronic lymphocytic leukemia (CLL) who are on a BTK inhibitor (such as ibrutinib or zanubrutinib) but still have detectable cancer in their blood. **You may be eligible if...** - You are between 18 and 80 years old - You have been diagnosed with CLL or small lymphocytic lymphoma (SLL) - You have been taking a BTK inhibitor (ibrutinib, zanubrutinib, orelabrutinib, or acalabrutinib) for more than 6 months and have responded (partial or complete response) - Residual cancer cells are still detectable in your blood by a sensitive test - Your kidney and liver function meet the study requirements **You may NOT be eligible if...** - Your CLL/SLL has not responded to the BTK inhibitor - You have certain genetic mutations in your cancer (e.g., BCL2 G101V) that predict resistance to venetoclax - You have serious infections or other major health conditions - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGVenetoclax combined with Ibrutinib

All Patients will be treated with venetoclax for 12 cycles after a standard 5-week dose ramp-up, as an add-on to the primary using ibrutinib. After the completion of combination therapy, patients will stop both the ibrutinib and venetoclax then be followed. Each cycle is 28 days. At the start of cycle 0, patients will start venetoclax by 20mg-50mg-100mg-200mg daily in a weekly dose escalation way. The combination of full dose venetoclax (400mg) and ibrutinib will continue for an additional 12 cycles. Venetoclax and ibrutinib will be continued until the completion of cycle 12, start of new CLL-directed therapies, disease progression or unacceptable toxicities, depending on which comes first. Ibrutinib is intended to be admistratered orally 420mg once daily.

DRUGVenetoclax combined with Zanubrutinib

All Patients will be treated with venetoclax for 12 cycles after a standard 5-week dose ramp-up, as an add-on to the primary using zanubrutinib. After the completion of combination therapy, patients will stop both the zanubrutinib and venetoclax then be followed. Each cycle is 28 days. At the start of cycle 0, patients will start venetoclax by 20mg-50mg-100mg-200mg daily in a weekly dose escalation way. The combination of full dose venetoclax (400mg) and zanubrutinib will continue for an additional 12 cycles. Venetoclax and zanubrutinib will be continued until the completion of cycle 12, start of new CLL-directed therapies, disease progression or unacceptable toxicities, depending on which comes first. Zanubrutinib is intended to be admistratered orally 160mg twice daily.

DRUGVenetoclax combined with Acalabrutinib

All Patients will be treated with venetoclax for 12 cycles after a standard 5-week dose ramp-up, as an add-on to the primary using acalabrutinib. After the completion of combination therapy, patients will stop both the acalabrutinib and venetoclax then be followed. Each cycle is 28 days. At the start of cycle 0, patients will start venetoclax by 20mg-50mg-100mg-200mg daily in a weekly dose escalation way. The combination of full dose venetoclax (400mg) and acalabrutinib will continue for an additional 12 cycles. Venetoclax and acalabrutinib will be continued until the completion of cycle 12, start of new CLL-directed therapies, disease progression or unacceptable toxicities, depending on which comes first. Acalabrutinib is intended to be admistratered orally 100mg twice daily.

DRUGVenetoclax combined with Orelabrutinib

All Patients will be treated with venetoclax for 12 cycles after a standard 5-week dose ramp-up, as an add-on to the primary using orelabrutinib. After the completion of combination therapy, patients will stop both the orelabrutinib and venetoclax then be followed. Each cycle is 28 days. At the start of cycle 0, patients will start venetoclax by 20mg-50mg-100mg-200mg daily in a weekly dose escalation way. The combination of full dose venetoclax (400mg) and orelabrutinib will continue for an additional 12 cycles. Venetoclax and orelabrutinib will be continued until the completion of cycle 12, start of new CLL-directed therapies, disease progression or unacceptable toxicities, depending on which comes first. Orelabrutinib is intended to be admistratered orally 150mg once daily.


Locations(1)

Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital

Nanjing, Jiangsu, China

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NCT06958705


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