A prospective, open-label, multicenter randomized phase-II trial to evaluate the efficacy and safety of a sequential regimen of obinutuzumab (Gazyvaro) followed by obinutuzumab and venetoclax, followed by either standard venetoclax maintenance or MRD guided venetoclax maintenance in first-line patients with CLL and unfit for FCR-like regimens
Recruiting
- Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Registration Number
- NL-OMON23205
- Lead Sponsor
- HOVON data center
- Brief Summary
/A
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 70
Inclusion Criteria
Diagnosis of symptomatic CLL (according to IWCLL guidelines, including minimal required markers (CD5/CD19/CD23 triple positive with light chain restriction))
Patients without prior treatment for CLL (Corticoid treatment administered due to necessary immediate intervention is allowed; within the last 10 days before start of study treatment only dose equivalents of maximum 20 mg prednisolone are permitted);
Exclusion Criteria
♦ Current inclusion in other clinical trials
♦ Intolerance of exogenous protein administration;
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To separately study the efficacy, defined as MRD negative bone marrow and no progression according to the IWCLL criteria, of the two arms of the study of either venetoclax maintenance or MRD-guided venetoclax maintenance after sequential regimens of obinutuzumab (pre-induction) followed by 6 cycles obinutuzumab with venetoclax and 6 cycles of venetoclax (induction) in first-line patients with CLL and unfit for FCR-like regimens.
- Secondary Outcome Measures
Name Time Method ♦ To determine efficacy as assessed by additional outcome measures, including overall response, PFS, event free survival (EFS), OS<br /><br>♦ To determine the impact of the study treatment on quality of life and geriatric scores (including a biological senescence marker of skin biopsy)<br /><br>♦ Toxicity of venetoclax after pre-induction, especially tumorlysis and neutropenia<br /><br>♦ To identify predictive factors for response and resistance mechanisms via:<br /><br>- Next-generation sequencing (NGS) at baseline and at progression<br /><br>- Flow-based subset analysis on expression levels of Bcl-2 proteins at baseline, during therapy and at progression<br /><br>- Analyses of malignant and non-malignant immune cells in PB and in LN at baseline and during treatment