Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western adults, where abnormal B lymphocytes accumulate in the blood, bone marrow, and lymph nodes. It grows slowly and many patients live years without needing treatment — but when treatment is needed, targeted oral drugs have largely replaced chemotherapy.
What's actually going on in research
BTK inhibitors like ibrutinib and acalabrutinib and the BCL-2 inhibitor venetoclax have transformed CLL treatment, producing deep remissions with far fewer side effects than traditional chemotherapy. Fixed-duration combination therapy with venetoclax plus obinutuzumab achieves minimal residual disease negativity in many patients, potentially allowing treatment-free periods. Covalent and non-covalent BTK inhibitors are being tested for patients who develop resistance to first-generation agents.
Fixed-duration venetoclax
Combining the BCL-2 inhibitor venetoclax with anti-CD20 antibodies for a defined 12–24 months achieves deep remissions that can last years after stopping therapy.
Next-generation BTK inhibitors
Non-covalent BTK inhibitors like pirtobrutinib overcome resistance to ibrutinib and acalabrutinib. Trials are testing them in BTK-resistant patients and as first-line therapy.
Minimal residual disease guided therapy
Trials are using ultra-sensitive MRD testing to decide when to stop treatment and when to extend it, tailoring therapy duration to individual response.
What to know before you search
Eligibility depends on CLL treatment indication (Rai/Binet stage, symptoms), del(17p) or TP53 mutation status, prior BTK or venetoclax exposure, and MRD status.
What types of trials are currently open
- Treatment trials — Testing new BTK inhibitor, venetoclax, or antibody combinations in previously untreated CLL.
- Relapsed CLL trials — Evaluating options after BTK inhibitor or venetoclax failure, including non-covalent BTK inhibitors and CAR-T.
- Watch-and-wait trials — Testing early intervention strategies versus observation in asymptomatic early-stage CLL.
- MRD-guided trials — Using minimal residual disease testing to individualize treatment duration.
- High-risk CLL trials — Testing intensified approaches for patients with del(17p), TP53 mutation, or complex karyotype.
Recently added Chronic Lymphocytic Leukemia trials
Impact of Targeted Therapy on Cancer-Related Cognitive Impairment
This study examines whether there are differences in brain health or well-being in patients receiving TKI therapy for leukemia compared to individuals who do not receive TKI therapy.
A Real-world Study of Ibrutinib and Venetoclax (I+V) First-Line Treatment Given for Fixed-duration of Time in Participants With Chronic Lymphocytic Leukemia
The purpose of this study is to see how well Ibrutinib and Venetoclax (I+V) treatment works (effectiveness) for participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) when it is used in routine, everyday medical care.
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