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Chronic Lymphocytic LeukemiaPhase 2ZEN-CLLNCT07739459

Study of Zanubrutinib in Older Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL)

A Phase 2 study testing Zanubrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by The Lymphoma Academic Research Organisation at 17 sites in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II, open-label, multicenter study evaluates zanubrutinib in patients aged 80 years and older with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who require treatment. CLL and SLL are slow-growing blood cancers that mainly affect older adults. Read more about this study

Who is it for?
Ages 80 years and older
What is being tested?
Zanubrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
17 sitesFrance
Study dates
Dec 2026to Dec 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 80 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • Any prior CLL or SLL-specific therapies, even including rituximab used for autoimmune cytopenias.
  • Clinically significant cardiovascular disease including the following:
  • Myocardial infarction within 6 months prior to ICF signature
  • Unstable angina within 3 months prior to ICF signature
  • NYHA class III or IV heart failure
  • Uncontrolled hypertension
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  • History of clinically significant arrhythmias (including sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes).
  • History of Mobitz II second- or third-degree heart block without permanent pacemaker
  • 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:
  • Non-invasive basal cell or epidermoid carcinoma (non melanoma)
  • In situ carcinoma of the cervix
  • In situ carcinoma of the breast
  • Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis [TNM] clinical staging system
  • 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

Trial locations and contacts

17 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Project management contact

+33 4 72 66 93 33

zen-cll@lysarc.org

17 sites in 1 country

France17 sites

  • Ch Victor Dupouy

    Argenteuil, 95107

    Driss CHAOUI, doctor, driss.chaoui@ch-argenteuil.fr

    Driss CHAOUI, doctor

  • Ch D'Avignon - Hopital Henri Duffaut

    Avignon, 84000

    Safia CHEBREK, doctor, chebrek.safia@ch-avignon.fr

    Safia CHEBREK, doctor

  • Ch de La Cote Basque

    Bayonne, 64109

    Nathan MOTTAL, doctor, nmottal@ch-cotebasque.fr

    Nathan MOTTAL, doctor

  • Institut Bergonie

    Bordeaux, 33076

    Fontanet BIJOU, doctor, f.bijou@bordeaux.unicancer.fr

    Fontanet BIJOU, Doctor

  • Ch Rene Dubos

    Cergy-Pontoise, 95303

    Sinziana Ioana, doctor, sinziana-ioana.sarghi@ght-novo.fr

    Sinziana Ioana, doctor

  • Ch Sud Francilien

    Corbeil-Essonnes, 91106

    Laurence SIMON, doctor, laurence.simon@chsf.fr

    Laurence SIMON, doctor

  • Chu de Clermont-Ferrand

    Estaing, - SITE ESTAING

    Romain GUIEZE, doctor, rguieze@chu-clermontferrand.fr

    Romain GUIEZE, doctor

  • Chu de Grenoble

    Grenoble, 38700

    Lysiane MOLINA, doctor, lmolina@chu-grenoble.fr

    Lysiane MOLINA, doctor

  • Ch de Versailles - Hopital Andre Mignot

    Le Chesnay, 78157

    Fatiha MERABET, doctor, fmerabet@ght78sud.fr

    Fatiha MERABET, doctor

  • Ch Du Mans-Centre de Cancerologie de La Sarthe

    Le Mans, 72000

    Kamel LARIBI, doctor, klaribi@ch-lemans.fr

    Kamel LARIBI, doctor

  • Hopital Saint Vincent-de-Paul

    Lille, 59020

    Bénédicte HIVERT, doctor, hivert.benedicte@ghicl.net

    Bénédicte HIVERT, doctor

  • Chu Lyon-Sud

    Lyon, Pierre Bénite, 69310

    Emmanuelle FERRANT, doctor, emmanuelle.ferrant2@chu-lyon.fr

    Emmanuelle FERRANT, doctor

  • Centre Leon Berard

    Lyon, 69373

    Anne-Sophie MICHALLET, doctor, anne-sophie.michallet@lyon.unicancer.fr

    Anne-Sophie MICHALLET, doctor

  • Chu Orleans

    Orléans, 45067

    Marlène OCHMANN, doctor, marlene.ochmann@chu-orleans.fr

    Marlène OCHMANN, doctor

  • Centre Henri Becquerel

    Rouen, 76038

    Stéphane LEPRETRE, doctor, stephane.lepretre@chb.unicancer.fr

    Stéphane LEPRETRE, doctor

  • Iuct Oncopole

    Toulouse, 31059

    Loic YSEBAERT, professor, ysebaert.loic@iuct-oncopole.fr

    Loic YSEBAERT, professor

  • Chru Nancy - Hôpital Brabois

    Vandœuvre-lès-Nancy, 54511

    Pierre FEUGIER, professor, p.feugier@chru-nancy.fr

    Pierre FEUGIER, professor

Other trials in France

About this study

Official title: ZEN-CLL - A Phase II Trial Evaluating Zanubrutinib in Elderly, Treatment-Naïve, CLL Patients

This phase II, open-label, multicenter study evaluates zanubrutinib in patients aged 80 years and older with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who require treatment.

CLL and SLL are slow-growing blood cancers that mainly affect older adults. Although zanubrutinib is an effective treatment, taking it continuously at the full dose may increase the risk of side effects over time, particularly in elderly patients. The study aims to assess whether a planned reduction in the dose of zanubrutinib after an initial period of treatment can maintain disease control while improving long-term tolerability.

Read the detailed description

The ZEN-CLL study is evaluating a treatment strategy based on zanubrutinib in previously untreated elderly patients with CLL or small lymphocytic lymphoma (SLL). Approximately 95 participants will be enrolled in 17 LYSA centers in France.

All participants will receive zanubrutinib 160 mg twice daily for the first 18 months of treatment. After Month 18, the dose will be reduced according to the dose received at that time and the participant's tolerability. Treatment will continue until permanent treatment discontinuation or the end of study participation.

The study aims to determine whether this dose reduction strategy can maintain disease control while improving long-term tolerability in this elderly population.

Being tested
Zanubrutinib
Keywords
Chronic lymphocytic leukemia, Small lymphocytic lymphoma, Zanubrutinib, BTK inhibitor, First-line treatment, Treatment-naïve patients
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanubrutinibDrug

    Also called BRUKINSA

    Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor administered orally.

Study groups in NCT07739459
Study groupRoleWhat they receive
ZanubrutinibExperimentalParticipants will receive oral zanubrutinib followed by a predefined dose reduction strategy. Treatment will continue until disease progression, permanent treatment discontinuation, withdrawal of consent, loss to follow-up, or the end of study participation.
Receives: Drug: Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS)

    The primary endpoint is the Progression-Free Survival (PFS).

    Measured: 30 months and 5 years

Secondary outcomes (9)

  1. Permanent Treatment Discontinuation (PTD) Rate

    The key secondary endpoint is the rate of permanent treatment discontinuation (PTD).

    Measured: 18 months

  2. Overall Survival (OS)

    The secondary efficacy endpoint 1 is the Overall Survival (OS).

    Measured: At 30 months and at 5 years

  3. Time to Next Anti-Leukemia Treatment

    The secondary efficacy endpoint 2 is the Time to Next Anti-Leukemia Treatment (TTNLT).

    Measured: At 30 months and at 5 years

  4. Overall Response Rate

    The secondary efficacy endpoints 3 and 4 are Overall Response Rate (ORR) at 18 months and at 30 months, respectively.

    Measured: At 18 months and at 30 months

  5. Change From Baseline in Geriatric Assessment Scores

    Geriatric condition will be evaluated using minimal nurse-delivered scales recommended by the SIOG.

    Measured: at baseline, at 18 months, at 30 months and at 42 months

  6. Health-Related Quality of Life

    Health-Related Quality of Life as assessed by Questionnaire

    Measured: At baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.

  7. Frailty Assessment Score

    Frailty status will be assessed using a validated frailty scale.

    Measured: At baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.

  8. Patient-Reported Treatment Side Effect Burden

    Treatment side effect burden will be assessed using a patient-reported questionnaire.

    Measured: Baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.

  9. Incidence and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)

    Safety will be assessed by the incidence, severity, and seriousness of adverse events, including serious adverse events and adverse events of special interest.

    Measured: From first dose of study treatment until the end of study participation (up to 5 years).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2026
  2. Study startDec 2026 (estimated)
  3. Primary completionApr 2029 (estimated)
  4. Study completionDec 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
95 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07739459
Sponsor's protocol ID
ZEN-CLL
Other IDs
2025-525080-32-00, 2025
Acronym
ZEN-CLL
Status last verified
Jul 2026
First submitted
28 Jul 2026
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by The Lymphoma Academic Research Organisation at 17 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Project management (+33 4 72 66 93 33, zen-cll@lysarc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: 30 months and 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07739459.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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