NCT05478512

Front-line VenObi Combination Followed by Ven or VenZan Combination in Patients With Residual Disease: a MRD Tailored Treatment for Young Patients With High-risk CLL

Front-line Venetoclax and Obinutuzumab Combination Followed by Venetoclax or Venetoclax and Zanubrutinib Combination in Patients With Residual Disease: a Minimal Residual Disease (MRD) Tailored Treatment for Young Patients With High-risk CLL

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Multicentric phase 2 study for previously untreated high-risk CLL patients. Patients will receive 6 courses of the Venetoclax + Obinutuzumab combination. * Patients with stable disease or a response (CR/PR) with uMRD in the PB and BM at cycle 9 will continue treatment with Venetoclax single agent until cycle 13 and then stop treatment. * Patients with stable disease or a response (CR/PR) with evidence of residual disease in the PB and/or BM at cycle 9 will continue treatment with Venetoclax and Zanubrutinib combination until cycle 21. then, Patients with uMRD in the PB and BM at cycle 21 will stop treatment whereas patients with residual disease in the PB and/or BM at cycle 21 will discontinue Venetoclax and continue Zanubrutinib until disease progression.

Detailed description

This is a multicentric phase 2 study for previously untreated high-risk CLL patients. A. The study treatment will consist of 6 courses of the Venetoclax + Obinutuzumab combination. B. Patients with stable disease or a response (CR/PR) with undetectable MRD (uMRD) in the PB and BM at cycle 9 will continue treatment with Venetoclax single agent until cycle 13 and then stop treatment. C. Patients with stable disease or a response (CR/PR) with evidence of residual disease in the PB and/or BM at cycle 9 will continue treatment with Venetoclax and Zanubrutinib (VenZan) combination until cycle 21. c1. Patients with uMRD in the PB and BM at cycle 21 will stop treatment. c2. Patients with residual disease in the PB and/or BM at cycle 21 will discontinue Venetoclax and continue Zanubrutinib until disease progression. In all patients with uMRD, MRD will be monitored during the follow-up. Patients with a response with uMRD in the PB and BM who subsequently develop an MRD positivity will not be treated. A new treatment will start at the time of clinical disease progression according to the iwCLL criteria.

Conditions

• High Risk CLL
• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	VenObi+Ven or VenObi+VenZan	Patients will receive obinutuzumab 1000mg IV (cycle 1: day 1,8,15; Cycle2-6: day1) + venetoclax 400mg/d (preceded by a ramp-up phase) until cycle 9, day 28. At cycle9: * if uMRD = Venetoclax 400 mg/d orally until cycle 13. * if residual disease in the BM or PB = Venetoclax 400 mg/d + Zanubrutinib 160 mg orally twice daily until cycle 21. then, at cycle 21: * if uMRD = stop treatment * if residual disease in the BM or PB = zanubrutinib 160 mg orally twice daily until disease progression

Timeline

• Start date: 2023-07-21
• Primary completion: 2026-05-01
• Completion: 2027-07-01
• First posted: 2022-07-28
• Last updated: 2026-03-17

Locations

8 sites across 1 country: Italy