Can a gentler dose of zanubrutinib keep CLL at bay in the very elderly?
NCT ID NCT07739459
First seen Jul 31, 2026 · Last updated Sep 15, 2026 · Updated 2 times
Summary
This phase II trial is testing whether a planned dose reduction of the targeted therapy zanubrutinib can maintain control of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) while reducing long-term side effects in patients aged 80 and older who have not yet received treatment. The study will track how long the disease stays under control and how many patients need to stop treatment permanently. The goal is to find a dosing strategy that balances effectiveness with tolerability for a particularly vulnerable age group.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- zanubrutinib (Brukinsa), an oral BTK inhibitor
- What this could lead to
- If successful, this could show that a lower maintenance dose of zanubrutinib keeps CLL controlled while being gentler for very elderly patients, potentially improving quality of life.
- What could go wrong
- This is a phase II trial with a modest number of participants, so results may not be definitive. Reducing the dose could also reduce effectiveness, and side effects may still occur.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
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About 95 people
The number the study aims to enrol. It can still change while the study runs.
- Expected to start
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Dec 2026
An estimate. Start dates often move.
- Expected to finish
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Dec 2032
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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80 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * Participant who understands and voluntarily signs and dates an informed consent form prior to any studyspecific assessments/procedures being conducted, including consent for specific biology analysis * Must be able to adhere to the trial visit schedule and other protocol requirements * ≥ 80 years at the time of signing the informed consent form (ICF) with no upper age limit * Previously untreated and documented CLL or small lymphocytic lymphoma (SLL), with a Royal Marsden Hospital (RMH) or Matutes Score of 4 or 5. For SLL a detectable clone with a CLL phenotype in the peripheral blood is a prerequisite for trial participation. * Participant requiring treatment according to 2018 IWCLL guidelines * ECOG performance status 0 to 2 * Life expectancy \> 6 months * Adequate hematopoietic function within 7 days before the participant's enrollment * ANC ≥ 0.75 G/L * And Platelets ≥ 50 G/L Note: Platelets transfusions may be administered during screening to meet this requirement * Hemoglobin level \> 9g/dL, regardless of transfusion * Adequate renal function defined by a Creatinine Clearance ≥ 30 ml/min calculated according to MDRD or CKD-EPI or Cockcroft-Gault (using actual body weight). * Adequate liver function, as indicated by a total bilirubin \<1.5 x ULN, AST and ALT \<3 x ULN value, unless directly attributed to the participant's CLL/SLL or to Gilbert's Syndrome (the ULN is based on institutionalvalues) * Participant covered by any social security system * Participant who understands and speaks the country official language unless local regulation authorizes independent translator Exclusion Criteria: * Any prior CLL or SLL-specific therapies, even including rituximab used for autoimmune cytopenias. * Clinically significant cardiovascular disease including the following: 1. Myocardial infarction within 6 months prior to ICF signature 2. Unstable angina within 3 months prior to ICF signature 3. NYHA class III or IV heart failure 4. Uncontrolled hypertension 5. History of clinically significant arrhythmias (including sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes). 6. History of Mobitz II second- or third-degree heart block without permanent pacemaker 7. Known LVEF \<50% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan * Child-Pugh liver cirrhosis * Clinical evidence for Central Nervous System involvement by CLL * Severe chronic obstructive lung disease with hypoxemia * Severe diabetes mellitus * Disease significantly affecting gastrointestinal function (malabsorption syndrome, stomach or small bowel resection) * Active or non-active autoimmune hemolytic anemia (AIHA) (isolated positive DAT is not an exclusion criterion, but reticulocytes/haptoglobin levels must be in lab normal ranges) or idiopathic thrombocytopenic purpura (ITP), requiring steroid therapy with \> 20 mg daily of prednisone dose or equivalent. * Any prior history of Richter transformation or DLBCL * Any evidence or suspicion of Richter transformation or DLBCL during screening * Active malignancy other than the one treated in this trial. Prior history of malignancies unless the participant has been free of the disease for ≥ 2 years. However, participants with the following history /conditions that have been treated with a curative intent are allowed: 1. Non-invasive basal cell or epidermoid carcinoma (non melanoma) 2. In situ carcinoma of the cervix 3. In situ carcinoma of the breast 4. Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis \[TNM\] clinical staging system 5. Woman with adjuvant endocrine therapy (I.e., hormonotherapy) after breast cancer treatment can be enrolled if hormonotherapy was started for ≥ 2 years * History of stroke or intracranial hemorrhage within 6 months prior to ICF signature. * Major surgery 28 days before the ICF signature * History or known bleeding disorders (e.g hemophilia or von Willebrand disease) * Active Hepatitis C Virus (HCV) infection (RNA PCR-positive). Participants who received treatment for HCV infection that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable * Active Hepatitis B Virus (HBV) infection (DNA PCR-positive). Participants with evidence of prior HBV infection but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy during the entire treatment with active monitoring of viral load in the blood * Patient with a positive HIV test before enrollment are eligible provided that they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.Known or suspected hypersensitivity or anaphylaxis to trial intervention including active substance or to any of the excipients. * Requires or receiving anticoagulation with warfarin or dual antiplatelets therapy equivalent vitamin K antagonists (other anticoagulants allowed: novel oral anticoagulant alone, aspirin alone, heparin alone). * Requires treatment with a strong/moderate cytochrome CYP3A4 inhibitor/inducer. * Participation in another clinical study who would compromise the participation to the current study. * Vaccinated with live, attenuated vaccines within 6 months of ICF * Use of any standard or experimental anti-cancer drug therapy within 28 days before the start (Day 1) of study treatment * Corticosteroid use \> 20 mg per day within 1 week before the first dose of trial intervention, except as indicated for other medical conditions, such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of trial intervention or contrast. * Any significant medical conditions, or laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical trial or affect interpretation of trial outcomes (according to the investigator's decision) * Any uncontrolled and/or active significant infection (eg, bacterial, viral, or fungal; including participants with positive cytomegalovirus PCR). * Participant deprived of their liberty by a judicial or administrative decision * Participant hospitalized without consent * Adult participant under legal protection
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
17 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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Centre Henri Becquerel
Rouen, 76038, France
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Centre Leon Berard
Lyon, 69373, France
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Ch D'Avignon - Hopital Henri Duffaut
Avignon, 84000, France
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Ch Du Mans-Centre de Cancerologie de La Sarthe
Le Mans, 72000, France
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Ch Rene Dubos
Cergy-Pontoise, 95303, France
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Ch Sud Francilien
Corbeil-Essonnes, 91106, France
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Ch Victor Dupouy
Argenteuil, 95107, France
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Ch de La Cote Basque
Bayonne, 64109, France
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Ch de Versailles - Hopital Andre Mignot
Le Chesnay, 78157, France
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Chru Nancy - Hôpital Brabois
Vandœuvre-lès-Nancy, 54511, France
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Chu Lyon-Sud
Lyon, Pierre Bénite, 69310, France
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Chu Orleans
Orléans, 45067, France
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Chu de Clermont-Ferrand
Estaing, - SITE ESTAING, France
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Chu de Grenoble
Grenoble, 38700, France
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Hopital Saint Vincent-de-Paul
Lille, 59020, France
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Institut Bergonie
Bordeaux, 33076, France
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Iuct Oncopole
Toulouse, 31059, France
More trials for these conditions
Other studies related to the condition(s) this trial covers.
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- Can a new BTK inhibitor outsmart resistance in CLL?
- Can a new pill outsmart Drug-Resistant leukemia?
- Can engineered immune cells beat tough B-Cell cancers?
- Can a targeted drug outperform chemo for a common blood cancer?
- Can a triple drug combo outsmart High-Risk CLL?