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

9. september 2026 oppdatert av: The Lymphoma Academic Research Organisation

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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

95

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Frankrike
      • Argenteuil, Frankrike, 95107
      • Avignon, Frankrike, 84000
        • Ch D'Avignon - Hopital Henri Duffaut
        • Ta kontakt med:
        • Hovedetterforsker:
          • Safia CHEBREK, doctor
      • Bayonne, Frankrike, 64109
        • CH de la Côte Basque
        • Ta kontakt med:
        • Hovedetterforsker:
          • Nathan MOTTAL, doctor
      • Bordeaux, Frankrike, 33076
      • Cergy-Pontoise, Frankrike, 95303
      • Corbeil-Essonnes, Frankrike, 91106
        • Ch Sud Francilien
        • Ta kontakt med:
        • Hovedetterforsker:
          • Laurence SIMON, doctor
      • Estaing, Frankrike, - SITE ESTAING
      • Grenoble, Frankrike, 38700
        • CHU de GRENOBLE
        • Ta kontakt med:
        • Hovedetterforsker:
          • Lysiane MOLINA, doctor
      • Le Chesnay, Frankrike, 78157
        • Ch de Versailles - Hopital Andre Mignot
        • Ta kontakt med:
        • Hovedetterforsker:
          • Fatiha MERABET, doctor
      • Le Mans, Frankrike, 72000
        • Ch Du Mans-Centre de Cancerologie de La Sarthe
        • Ta kontakt med:
        • Hovedetterforsker:
          • Kamel LARIBI, doctor
      • Lille, Frankrike, 59020
        • Hopital Saint Vincent-de-Paul
        • Ta kontakt med:
        • Hovedetterforsker:
          • Bénédicte HIVERT, doctor
      • Lyon, Frankrike, 69373
      • Orléans, Frankrike, 45067
      • Rouen, Frankrike, 76038
      • Toulouse, Frankrike, 31059
      • Vandœuvre-lès-Nancy, Frankrike, 54511
        • CHRU Nancy - hôpital Brabois
        • Ta kontakt med:
        • Hovedetterforsker:
          • Pierre FEUGIER, professor
    • Pierre Bénite
      • Lyon, Pierre Bénite, Frankrike, 69310

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Zanubrutinib
Participants 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.
Legemiddel: Zanubrutinib
Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor administered orally.
Andre navn:
  • BRUKINSA

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-Free Survival (PFS)
Tidsramme: 30 months and 5 years
The primary endpoint is the Progression-Free Survival (PFS).
30 months and 5 years

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Permanent Treatment Discontinuation (PTD) Rate
Tidsramme: 18 months
The key secondary endpoint is the rate of permanent treatment discontinuation (PTD).
18 months
Overall Survival (OS)
Tidsramme: At 30 months and at 5 years
The secondary efficacy endpoint 1 is the Overall Survival (OS).
At 30 months and at 5 years
Time to Next Anti-Leukemia Treatment
Tidsramme: At 30 months and at 5 years
The secondary efficacy endpoint 2 is the Time to Next Anti-Leukemia Treatment (TTNLT).
At 30 months and at 5 years
Overall Response Rate
Tidsramme: At 18 months and at 30 months
The secondary efficacy endpoints 3 and 4 are Overall Response Rate (ORR) at 18 months and at 30 months, respectively.
At 18 months and at 30 months
Change From Baseline in Geriatric Assessment Scores
Tidsramme: at baseline, at 18 months, at 30 months and at 42 months
Geriatric condition will be evaluated using minimal nurse-delivered scales recommended by the SIOG.
at baseline, at 18 months, at 30 months and at 42 months
Health-Related Quality of Life
Tidsramme: At baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.
Health-Related Quality of Life as assessed by Questionnaire
At baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.
Frailty Assessment Score
Tidsramme: At baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.
Frailty status will be assessed using a validated frailty scale.
At baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.
Patient-Reported Treatment Side Effect Burden
Tidsramme: Baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.
Treatment side effect burden will be assessed using a patient-reported questionnaire.
Baseline, every 3 months for the first 2 years, and every 6 months thereafter for 3 years.
Incidence and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
Tidsramme: From first dose of study treatment until the end of study participation (up to 5 years).
Safety will be assessed by the incidence, severity, and seriousness of adverse events, including serious adverse events and adverse events of special interest.
From first dose of study treatment until the end of study participation (up to 5 years).

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

The Lymphoma Academic Research Organisation

Samarbeidspartnere

Lymphoma Study Association
BeOne Medicines

Etterforskere

  • Hovedetterforsker: Loïc YSEBAERT, Professor, IUCT Oncopole
  • Hovedetterforsker: Emmanuelle FERRANT, Doctor, Hospices Civils de Lyon

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. desember 2026

Primær fullføring (Antatt)

1. april 2029

Studiet fullført (Antatt)

1. desember 2032

Datoer for studieregistrering

Først innsendt

28. juli 2026

Først innsendt som oppfylte QC-kriteriene

28. juli 2026

Først lagt ut (Faktiske)

31. juli 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

14. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

9. september 2026

Sist bekreftet

1. juli 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ZEN-CLL
  • 2025 (U.S. NIH-stipend/kontrakt: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
  • 2025-525080-32-00 (Ctis)

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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