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

NCT04963946 | Active Not Recruiting Phase 2

• 1 other identifier: FILOCLL14 - STAIR
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 32

Brief Summary

The irreversible Bruton's Tyrosine Kinase (BTK) inhibitor acalabrutinib (ACA) has potent clinical activity as a single agent in patients with treatment naive and Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL). However, a growing body of concerns is raising regarding the unlimited administration of targeted therapy as BTKi. First, long-term treatments expose the patients to increased risk of specific adverse events (infections, bleeding events or cardiovascular problems). Second, continuous administration might also increase the risk of clonal evolution and therapeutic resistance resulting from genetic alterations such as BTK or PLCG2 mutations. Discontinuation of therapy after a fixed period is expected to prevent these events. Rapid and deep responses yielded by ACA in elderly patients pave the way of investigating a limited 18-months period schedule. This study aims to investigate the 1-year PFS upon ACA discontinuation and efficacy of restarting ACA upon symptomatic relapse.

Conditions

Untreated Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) at one year after acalabrutinib interruption

  Time from randomization (M19 : discontinuation of acalabrutinib after of 18 months treatment) to progression (needing therapy or not) or death from any cause

  until 12 months after acalabrutinib interruption

Study Arms (2)

watch and monitor

EXPERIMENTAL

After 18 months of acalabrutinib treatment, patients will stop acalabrutinib treatment for watch and monitor until month 60. If progression disease, patients will be re-treated with ACA at the last received dose after central reviewing of treatment criteria.

Drug: Stop ACA

Acalabrutinib

ACTIVE COMPARATOR

After 18 months of acalabrutinib treatment, patients will continue acalabrutinib treatment until month 60. If progression disease or unacceptable toxicity, patients will receive next line therapy at the discretion of their physicians and according to iwCLL 2018 criteria

Drug: ACA Continuation

Interventions

Stop ACA DRUG

discontinuation of acalabrutinib after 18 months in treatment-naïve CLL patients

watch and monitor

ACA Continuation DRUG

continuation of acalabrutinib at the same dose

Acalabrutinib

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.
• 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
• 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

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead

Study Sites (32)

Chu Angers

Angers, 49933, France

Location

ARGENTEUIL - Centre hospitalier Victor Dupouy

Argenteuil, France

Location

Ch Avignon

Avignon, 84000, France

Location

Ch Cote Basque

Bayonne, 64109, France

Location

BOBIGNY - Hôpital Avicenne

Bobigny, France

Location

Hôpital Privé Sévigné

Cesson-Sévigné, 35510, France

Location

CHU Estaing - Hématologie Clinique Adulte

Clermont-Ferrand, 63000, France

Location

Corbeil-Essonnes -

Corbeil-Essonnes, France

Location

CHU Grenoble - Hématologie

Grenoble, 388043, France

Location

Centre Hospitalier du Mans

Le Mans, 72000, France

Location

Hôpital Saint Vincent de Paul

Lille, 59000, France

Location

Centre Léon Bérard - Hématologie

Lyon, 69373, France

Location

Institut Paoli-Calmettes - Hématologie Clinique

Marseille, 13273, France

Location

Centre Hospitalier Regional Metz Thionville

Metz, 57085, France

Location

Hôpital Saint-Eloi - Hématologie Clinique

Montpellier, 34295, France

Location

Hopital E.Muller

Mulhouse, 68100, France

Location

CHR ORLEANS - Hématologie

Orléans, 44100, France

Location

Hopital Pitie Salpetriere Service Hematologie Clinique - Pavillon de L'Enfant Et Adolescent

Paris, 75651, France

Location

CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique

Perpignan, 66000, France

Location

Bordeaux Pessac

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire

Poitiers, 86021, France

Location

CERGY-PONTOISE - Centre Hospitalier René Dubos

Pontoise, France

Location

Chu Reims

Reims, 51092, France

Location

CHU Pontchaillou - Hématologie Clinique BMT-HC

Rennes, 35033, France

Location

Centre Henri Becquerel - Service Hématologie Clinique

Rouen, 76038, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42271, France

Location

IUCT ONCOPOLE - Hématologie

Toulouse, 31059, France

Location

Hôpital Bretonneau - Hématologie et Thérapie Cellulaire

Tours, 37044, France

Location

CHU Nancy Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Vannes - Chba

Vannes, France

Location

VERSAILLES - Hôpital André Mignot

Versailles, France

Location

Study Officials

• Loïc Ysebaert, Pr

  French Innovative Leukemia Organisation

  PRINCIPAL INVESTIGATOR

• Romain GUIEZE, Pr

  French Innovative Leukemia Organisation

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: multicenter, non comparative, randomized, stop and restart

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 15, 2021
• Study Start: October 18, 2021
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (32)