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Stopping and restarting a medication for elderly patients with untreated chronic lymphocytic leukemia

STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia

Phase 2 Interventional French Innovative Leukemia Organisation · NCT04963946

This study is testing whether older patients with untreated chronic lymphocytic leukemia can safely stop taking the medication acalabrutinib for a while and see if they can restart it later if needed.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment160 (estimated)
Ages70 Years and up
SexAll
SponsorFrench Innovative Leukemia Organisation Academic / other
Drugs / interventionsradiation, acalabrutinib
Locations32 sites (Angers and 31 other locations)
Trial IDNCT04963946 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effects of a stopping strategy for the medication acalabrutinib in patients over 70 years old or with significant comorbidities who have untreated chronic lymphocytic leukemia (CLL). Patients will receive acalabrutinib for 18 months, after which they will be randomized to either continue treatment or undergo monitoring without the medication. The study aims to assess progression-free survival (PFS) after stopping the drug and the efficacy of restarting it if symptoms return. The trial also includes monitoring for adverse effects and disease progression throughout the study period.

Who should consider this trial

Good fit: Ideal candidates are patients aged over 70 with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma and significant comorbidities.

Not a fit: Patients with severe cardiovascular issues or those on certain anticoagulant therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could reduce the risks associated with long-term targeted therapy while maintaining effective disease management.

How similar studies have performed: While there is growing interest in treatment interruption strategies, this specific approach to acalabrutinib in elderly CLL patients is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Age \> 70 years or older
* Eastern Cooperative Oncology Group (ECOG) performance status \< 2
* Previously untreated CLL or Small Lymphocytic Lymphoma (SLL)
* CLL or SLL requiring treatment according to the iwCLL 2018 criteria2
* Total Cumulative Illness Rating Scale (CIRS) score \> 6 or 30 \< CrCl \< 69 mL/min
* Both patients with or without TP53 disruption 17p deletion and/or TP53 mutations) can be included
* Patients can be included whatever their IGHV mutational status
* Patients with therapy-controlled cardiovascular comorbidities and/or anticoagulation (novel oral anticoagulant alone, aspirin alone, heparin alone) can be included (patients treated by vitamin K antagonist or dual anti-platelet therapy cannot be included)
* Life expectancy \> 6 months
* Adequate hematology values: absolute neutrophil count ≥ 0.75 x 109/L, platelet count ≥ 50 x 109/L.
* Adequate liver function as indicated by a total bilirubin \<1.5, aspartate transaminase and alanine transaminase ≤3 the institutional upper limits of normal values, unless directly attributable to CLL
* Signed (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including specify biology analysis, and are willing to participate in the study.

Exclusion Criteria:

* Known HIV seropositivity
* Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

  * Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
  * Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with subjects who are on ongoing anti-infective treatment and subjects who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study treatment

    1. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus Polymerase Chain Reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded.
    2. Subjects who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enrollment. Those who are hepatitis C virus PCR positive will be excluded
  * Active and uncontrolled autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) (isolated positive Direct Antiglobulin Testing (DAT) is not an exclusion criteria) and idiopathic thrombocytopenic purpura (ITP).
  * Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.
* Patients treated by vitamin K antagonist or dual anti-platelet therapy
* History of bleeding diathesis (e.g. hemophilia or von Willebrand disease)
* History of confirmed progressive multifocal leukoencephalopathy (PML).
* Concurrent severe diseases which exclude the administration of therapy :

  * heart insufficiency New York Heart Association (NYHA) grade III/IV, Left Ventricular Ejection Fraction (LEVF) \< 50% and or Recirculation Fraction (RF) \< 30%, myocardial infarction within the past 6 months prior to study
  * Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional (Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study)
  * severe chronic obstructive lung disease with hypoxemia
  * history of stroke or intra-cranial hemorrhage within the last 6 months
  * severe diabetes mellitus
  * uncontrolled hypertension
  * impaired renal function with creatinine clearance \< 30 ml/min according the formula of Cockcroft and Gault
  * Patient who requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study.
* Disease significantly affecting gastrointestinal function (malabsorption syndrome, stomach or small bowel resection)
* Evidence for Richter syndrome
* Treatment with any of the following within 7 days prior to the first dose of study drug: steroid therapy for anti-neoplastic intent.
* A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the patient's participation in this study or interpretation of study outcomes
* Major surgery within 30 days prior to the first dose of study treatment.
* History of prior other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following:

  * curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study.
  * other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥ 5 years without further treatment
* Adult under law-control
* Fertile male patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study
* No affiliation to social security

Where this trial is running

Angers and 31 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Untreated Chronic Lymphocytic Leukemia
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.