Chronic Lymphocytic Leukemia Clinical Trials (April 2026): 228 Recruiting Interventional Studies
Last updated: April 22, 2026
Current Clinical Trial Landscape
Active research areas in 2026:
- Non-covalent BTK inhibitors: pirtobrutinib replacing ibrutinib (BRUIN Phase 3 data)
- BTK degraders: NX-5948, BGB-16673 — overcoming all BTK resistance mutations
- Next-gen BCL-2 inhibitors: sonrotoclax, lisaftoclax — replacing venetoclax
- Fixed-duration BTK+BCL-2 combinations (pirtobrutinib + venetoclax, sonrotoclax + zanubrutinib)
- Bispecific antibodies as consolidation therapy
- Early treatment for high-risk CLL (before symptoms)
Standard of care: First-line: BTK inhibitor continuous (ibrutinib, acalabrutinib, zanubrutinib) OR fixed-duration venetoclax + obinutuzumab. Second-line: sequence depends on first-line — venetoclax after BTKi, or BTKi after venetoclax. del(17p)/TP53 and IGHV status guide treatment choice.
Recruiting Trials by Treatment Setting
Treatment-Naïve (First-Line)
Testing next-gen agents and fixed-duration combos as first-line:
- Next-gen BTK inhibitors:
- NCT05254743 - Pirtobrutinib vs ibrutinib in treatment-naïve CLL (Phase 3)
- NCT06136559 - Nemtabrutinib vs investigator's choice in CLL (Phase 3)
- Fixed-duration combinations:
- NCT07277231 - Sonrotoclax + zanubrutinib vs venetoclax + obinutuzumab in treatment-naïve CLL (Phase 3)
- NCT05197192 - Acalabrutinib + obinutuzumab + venetoclax vs obinutuzumab + venetoclax (Phase 3)
- NCT06378138 - ICP-248 + orelabrutinib in treatment-naïve CLL (Phase 3)
- NCT06319456 - Lisaftoclax + acalabrutinib vs immunochemotherapy in CLL (Phase 3)
Relapsed / Refractory — After BTK Inhibitor
After covalent BTK inhibitor failure — non-covalent BTKi, BTK degraders, and BCL-2 combos:
- BTK degraders (overcomes all resistance mutations):
- NCT07516093 - NX-5948 vs pirtobrutinib in R/R CLL/SLL (Phase 3)
- NCT06846671 - BGB-16673 vs investigator's choice in R/R CLL (Phase 3)
- NCT06973187 - BGB-16673 vs pirtobrutinib in R/R CLL (Phase 3)
- NCT06970743 - BGB-16673 vs investigator's choice in cBTKi-pretreated R/R CLL (Phase 3)
- Non-covalent BTK inhibitors:
- NCT07342478 - Rocbrutinib vs pirtobrutinib in cBTKi-pretreated R/R CLL (Phase 3)
- NCT07139873 - DZD8586 vs investigator's choice in R/R CLL/SLL (Phase 3)
- Nemtabrutinib combinations:
- NCT05947851 - Nemtabrutinib + venetoclax vs venetoclax + rituximab in second-line CLL (Phase 3)
Next-Gen BCL-2 Combinations
Sonrotoclax and lisaftoclax aim to replace venetoclax with better efficacy/safety:
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- NCT06943872 - Sonrotoclax + obinutuzumab in CLL (Phase 3)
- NCT06428019 - TLS risk evaluation with venetoclax in CLL (Phase 3)
- NCT07082452 - Reduced venetoclax exposure time in CLL (Phase 3)
- NCT06104566 - Lisaftoclax (APG-2575) for CLL/SLL (Phase 3)
Bispecific Consolidation
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- NCT07509151 - Surovatamig as consolidation therapy in CLL (Phase 3)
Early Treatment (High-Risk CLL)
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- NCT04269902 - Testing early treatment for high-risk CLL (Phase 3)
Richter Transformation
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- NCT07220187 - Pirtobrutinib added to standard treatment for newly diagnosed Richter transformation (Phase 3)
- NCT07321652 - Sonrotoclax + zanubrutinib for CLL including Richter (Phase 3)
Showing selected notable trials. View all 228 recruiting interventional trials on ClinicalTrials.gov.
Frequently Asked Questions
How do I find CLL clinical trials I'm eligible for?
Enter your CLL details into ClinTrialFinder — including del(17p)/TP53 status, IGHV mutation status, prior BTK inhibitor and venetoclax exposure, and Rai/Binet stage. The AI matches you with trials in minutes.
What CLL trials are currently recruiting?
There are 228 recruiting interventional trials for CLL including next-gen BTK inhibitors (pirtobrutinib), BTK degraders (NX-5948, BGB-16673), BCL-2 combinations (sonrotoclax, lisaftoclax), bispecific consolidation, and early treatment for high-risk CLL.
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