NCT04523428

REtreatment With VEnetoclax and Acalabrutinib After Venetoclax Limited Duration (REVEAL)

A Prospective, Multicenter, Phase-II Trial of Venetoclax Plus Acalabrutinib in Patients Who Have Relapsed After First Line Venetoclax + Anti-CD20 mAb Treatment for Chronic Lymphocytic Leukemia (CLL or SLL)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Fixed-duration regimens containing combinations of venetoclax with CD20 targeting agents are expected to soon become standard practice in first-line patients with chronic lymfocytic leukemia (CLL). The advantage of a fixed duration venetoclax combination as part of first-line treatment is the potential to retreat with venetoclax in patients who develop relapsed disease after a treatment free period. However, efficacy of venetoclax retreatment following a fixed duration venetoclax combination is still hypothetical as clinical data are lacking. Thus, there is an urgent need for data proving efficacy of venetoclax combinations following venetoclax treatment cessation. Testing of a novel venetoclax-containing regimen for relapsed CLL without the repeat of anti-CD20 monoclonal antibody (mAb) is a rational approach.

Detailed description

First-line venetoclax and CD20 antibody containing regimens that are currently being tested are based on either a fixed duration schedule or on an MRD-based time-limited schedule. The assumption of these regimens is that, aside from the deep (often uMRD) and often longstanding remissions, relapsed disease can be retreated with a venetoclax-based regimen. This, however, has not been formally proven. In this study, patients who received a first line regimen with either venetoclax and rituximab (GAIA/CLL13/HOVON 140 trial, \[NCT02950051\] ) or venetoclax and the second generation anti-CD20 antibody obinutuzumab (GAIA/CLL13/HOVON 140 trial, and the HOVON139 trial \[Netherlands Trial Registry ID number #NTR6043\]) and have relapsed with the need for a subsequent treatment are eligible to enter the study and to receive a combination of venetoclax with the highly selective BTK inhibitor acalabrutinib. Combination of venetoclax with acalabrutinib is expected to lead to uMRD, making discontinuation of therapy possible.

Conditions

• CLL/SLL

Interventions

Type	Name	Description
DRUG	Venetoclax/Acalabrutinib	All patients will receive a lead-in with 2 cycles of acalabrutinib 100 mg bid. Hereafter patients will continue with ramp-up of venetoclax followed by daily 400 mg venetoclax in combination with acalabrutinib for 24 cycles. Patients will be treated until they have received a total of 26 cycles or until progression, whichever comes first.

Timeline

• Start date: 2020-12-23
• Primary completion: 2028-12-01
• Completion: 2032-12-01
• First posted: 2020-08-21
• Last updated: 2026-01-06

Locations

18 sites across 3 countries: Belgium, Denmark, Netherlands