155 CLL Clinical Trials Recruiting Now (May 2026): Chronic Lymphocytic Leukemia — BTK Inhibitors, BTK Degraders, Venetoclax, BCL-2, Acalabrutinib

Last updated: May 27, 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):
- NCT06846671 - CaDAnCe-302: BGB-16673 vs investigator's choice in R/R CLL (Phase 3, BeOne Medicines)
- NCT06973187 - BGB-16673 vs pirtobrutinib in R/R CLL (Phase 3)
- NCT06970743 - CaDAnCe-303: BGB-16673 vs investigator's choice in cBTKi-pretreated R/R CLL (Phase 3, BeOne Medicines)
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:

- NCT06943872 - Sonrotoclax + obinutuzumab in CLL (Phase 3)
- NCT06428019 - TLS risk evaluation with venetoclax in CLL (Phase 3, AbbVie)
- NCT06104566 - Lisaftoclax (APG-2575) global Phase 3 for CLL/SLL (Ascentage Pharma)

Early Treatment (High-Risk CLL)

Treating early in patients with high-risk genetics or infection risk, before standard IWCLL treatment criteria are met:

NCT04269902 - Testing early treatment for high-risk CLL (Phase 3, NCI)
NCT03868722 - Short-term acalabrutinib + venetoclax in newly diagnosed CLL with high risk of infection or early treatment, in patients who do not yet meet IWCLL treatment criteria (Phase 2/3, Rigshospitalet Denmark)

Bispecific Consolidation & Richter Transformation

No Phase 3 currently recruiting in either subspace as of May 2026 — multiple Phase 3 trials (surovatamig consolidation, pirtobrutinib + standard treatment for Richter, sonrotoclax + zanubrutinib including Richter) are filed as NOT_YET_RECRUITING and expected to open in coming months. Earlier-phase Richter trials may be available; search the full CLL trial list below for current options.

Showing selected notable trials. View all 155 recruiting interventional trials on ClinicalTrials.gov (corpus count, May 2026).

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 155 recruiting interventional trials for CLL in May 2026, including next-gen BTK inhibitors (pirtobrutinib, rocbrutinib, DZD8586), BTK degraders (BGB-16673), BCL-2 combinations (sonrotoclax, lisaftoclax), acalabrutinib + venetoclax fixed-duration, and early treatment for high-risk or high-infection-risk CLL.

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