Venetoclax as Consolidation in CLL Patients Treated With BTK Inhibitor Monotherapy

Sponsor
The First Affiliated Hospital with Nanjing Medical University
Study ID
NCT06958705
Phase
PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax combined with Ibrutinib — DRUG
    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.
  • Venetoclax combined with Zanubrutinib — DRUG
    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.
  • Venetoclax combined with Acalabrutinib — DRUG
    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.
  • Venetoclax combined with Orelabrutinib — DRUG
    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.

Study Details

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.

Key Dates

Start date
Dec 1, 2025
Status verified
Apr 2025
Primary completion
Dec 1, 2027
Completion
Feb 1, 2028

Study Design

Enrollment
79 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: CLL/SLL patients on ibrutinib monotherapy for ≥ 6 months
  • Experimental: CLL/SLL patients on zanubrutinib monotherapy for ≥ 6 months
  • Experimental: CLL/SLL patients on acalabrutinib monotherapy for ≥ 6 months
  • Experimental: CLL/SLL patients on orelabrutinib monotherapy for ≥ 6 months

Primary Outcome Measure

Rate of BM-uMRD after completion of combination therapy (Day 1 of Cycle 16) [ Time Frame: On Day 1 of Cycle 16 (each cycle is 28 days) ]

Central Contacts