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

NCT07739459 | Not Yet Recruiting Phase 2

• 2 other identifiers: ZEN-CLL2025-525080-32-00
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 17

Brief 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. 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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Chronic lymphocytic leukemia; Small lymphocytic lymphoma; Zanubrutinib; BTK inhibitor; First-line treatment; Treatment-naïve patients

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

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

  30 months and 5 years

Secondary Outcomes (9)

• Permanent Treatment Discontinuation (PTD) Rate

  18 months

• Overall Survival (OS)

  At 30 months and at 5 years

• Time to Next Anti-Leukemia Treatment

  At 30 months and at 5 years

• Overall Response Rate

  At 18 months and at 30 months

• Change From Baseline in Geriatric Assessment Scores

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

Study Arms (1)

Zanubrutinib

EXPERIMENTAL

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.

Drug: Zanubrutinib

Interventions

Zanubrutinib DRUG

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

Also known as: BRUKINSA

Zanubrutinib

Eligibility Criteria

• Age: 80 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)
• Any prior history of Richter transformation or DLBCL

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Lymphoma Study Association: collaborator
• BeOne Medicines: collaborator

Study Sites (17)

Chu Lyon-Sud

Lyon, Pierre Bénite, 69310, France

Location

Ch Victor Dupouy

Argenteuil, 95107, France

Location

Ch D'Avignon - Hopital Henri Duffaut

Avignon, 84000, France

Location

Ch de La Cote Basque

Bayonne, 64109, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Ch Rene Dubos

Cergy-Pontoise, 95303, France

Location

Ch Sud Francilien

Corbeil-Essonnes, 91106, France

Location

Chu de Clermont-Ferrand

Estaing, - SITE ESTAING, France

Location

Chu de Grenoble

Grenoble, 38700, France

Location

Ch de Versailles - Hopital Andre Mignot

Le Chesnay, 78157, France

Location

Ch Du Mans-Centre de Cancerologie de La Sarthe

Le Mans, 72000, France

Location

Hopital Saint Vincent-de-Paul

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Chu Orleans

Orléans, 45067, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Iuct Oncopole

Toulouse, 31059, France

Location

Chru Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Loïc YSEBAERT, Professor

  IUCT ONCOPOLE

  PRINCIPAL INVESTIGATOR

• Emmanuelle FERRANT, Doctor

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project management

CONTACT

+33 4 72 66 93 33; zen-cll@lysarc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: July 31, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): December 1, 2032
• Last Updated: July 31, 2026

Record last verified: 2026-07

Locations

FR (17)