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.
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
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:
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
zen-cll@lysarc.org+33 4 72 66 93 33
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.
Lyon, Pierre Bénite 69310, France
emmanuelle.ferrant2@chu-lyon.fr
driss.chaoui@ch-argenteuil.fr
chebrek.safia@ch-avignon.fr
nmottal@ch-cotebasque.fr
f.bijou@bordeaux.unicancer.fr
sinziana-ioana.sarghi@ght-novo.fr
laurence.simon@chsf.fr
rguieze@chu-clermontferrand.fr
lmolina@chu-grenoble.fr
fmerabet@ght78sud.fr
klaribi@ch-lemans.fr
hivert.benedicte@ghicl.net
anne-sophie.michallet@lyon.unicancer.fr
marlene.ochmann@chu-orleans.fr
stephane.lepretre@chb.unicancer.fr
ysebaert.loic@iuct-oncopole.fr
p.feugier@chru-nancy.fr
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