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

Starting soon · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

In brief

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.

Key facts

Study ID

NCT07739459

Run by

The Lymphoma Academic Research Organisation

People needed

95

Starts

2026-12-01

Expected to finish

2032-12-01

Last updated by the study team

2026-07-31

Who can join

Age: 80 and older. Sex: any. Healthy volunteers: not accepted.

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)
• 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.

Where it is running

• Chu Lyon-Sud — Lyon, Pierre Bénite, France
• Ch Victor Dupouy — Argenteuil, France
• Ch D'Avignon - Hopital Henri Duffaut — Avignon, France
• Ch de La Cote Basque — Bayonne, France
• Institut Bergonie — Bordeaux, France
• Ch Rene Dubos — Cergy-Pontoise, France
• Ch Sud Francilien — Corbeil-Essonnes, France
• Chu de Clermont-Ferrand — Estaing, France
• Chu de Grenoble — Grenoble, France
• Ch de Versailles - Hopital Andre Mignot — Le Chesnay, France
• Ch Du Mans-Centre de Cancerologie de La Sarthe — Le Mans, France
• Hopital Saint Vincent-de-Paul — Lille, France
• Centre Leon Berard — Lyon, France
• Chu Orleans — Orléans, France
• Centre Henri Becquerel — Rouen, France
• Iuct Oncopole — Toulouse, France
• Chru Nancy - Hôpital Brabois — Vandœuvre-lès-Nancy, France

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.