Informations générales (source: ClinicalTrials.gov)
STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia
Interventional
Phase 2
French Innovative Leukemia Organisation (Voir sur ClinicalTrials)
octobre 2021
août 2028
10 septembre 2025
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Avicenne | Vincent LEVY, Pr | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital La Pitié-Salpêtrière | Damien ROOS WEIL, Dr | Contact (sur clinicalTrials) | |||
| CH DE VERSAILLES SITE ANDRE MIGNOT | Fatiha MERABET, Dr | Contact (sur clinicalTrials) | |||
| HOPITAL NOVO | Driss CHAOUI | vendredi 5 septembre 2025 | Contact (sur clinicalTrials) | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Bordeaux Pessac - 33604 - Pessac - France | Marie-Sarah DILHUYDY, MD | Contact (sur clinicalTrials) | |||
| Centre Henri Becquerel - Service Hématologie Clinique - 76038 - Rouen - France | Stéphane LEPRETRE, Pr | Contact (sur clinicalTrials) | |||
| Centre Hospitalier du Mans - 72000 - Le Mans - France | Kamel LARIBI, Dr | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Lyon Sud - 69495 - Pierre-Bénite - France | Emmanuelle FERRANT, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Regional Metz Thionville - 57085 - Metz - France | Philippe CARASSOU, MD | Contact (sur clinicalTrials) | |||
| CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique - 66000 - Perpignan - France | Laurence SANHES, Dr | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - Hématologie - 69373 - Lyon - France | Anne-Sophie MICHALLET, Dr | Contact (sur clinicalTrials) | |||
| Ch Avignon - 84000 - Avignon - France | Safia CHEBREK, Dr | Contact (sur clinicalTrials) | |||
| Ch Cote Basque - 64109 - Bayonne - France | Julie GAY, MD | Contact (sur clinicalTrials) | |||
| CHR ORLEANS - Hématologie - 44100 - Orléans - France | Marlene OCHMANN, Dr | Contact (sur clinicalTrials) | |||
| Chu Angers - 49933 - Angers - France | Aline CLAVERT, MD | Contact (sur clinicalTrials) | |||
| CHU Estaing - Hématologie Clinique Adulte - 63000 - Clermont-Ferrand - France | Romain GUIEZE, Dr | Contact (sur clinicalTrials) | |||
| CHU Grenoble - Hématologie - 388043 - Grenoble - France | Lysiane MOLINA, Dr | Contact (sur clinicalTrials) | |||
| CHU Nancy Brabois - 54500 - Vandœuvre-lès-Nancy - France | Pierre FEUGIER, Pr | Contact (sur clinicalTrials) | |||
| CHU Pontchaillou - Hématologie Clinique BMT-HC - 35033 - Rennes - France | Sophie DE GUIBERT, Pr | Contact (sur clinicalTrials) | |||
| Chu Reims - 51092 - Reims - France | Anne QUINQUENEL, Dr | Contact (sur clinicalTrials) | |||
| Corbeil-Essonnes - - Corbeil-Essonnes - France | Laurence SIMON, Dr | Contact (sur clinicalTrials) | |||
| Hôpital Bretonneau - Hématologie et Thérapie Cellulaire - 37044 - Tours - France | Caroline DARTIGEAS, Dr | Contact (sur clinicalTrials) | |||
| Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire - 86021 - Poitiers - France | Cécile TOMOWIAK, Dr | Contact (sur clinicalTrials) | |||
| Hopital E.Muller - 68100 - Mulhouse - France | Bernard DRENOU, Dr | Contact (sur clinicalTrials) | |||
| Hôpital Privé Sévigné - 35510 - Cesson-Sévigné - France | Xavier CAHU, Dr | Contact (sur clinicalTrials) | |||
| Hôpital Saint Vincent de Paul - 59000 - Lille - France | Bénédicte HIVERT, Dr | Contact (sur clinicalTrials) | |||
| Hôpital Saint-Eloi - Hématologie Clinique - 34295 - Montpellier - France | Emanuelle TCHERNONOG, Dr | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie Lucien Neuwirth - 42271 - Saint-Priest-en-Jarez - France | Emilie CHALAYER, Dr | Contact (sur clinicalTrials) | |||
| Institut Paoli-Calmettes - Hématologie Clinique - 13273 - Marseille - France | Thérèse AURRAN, Dr | Contact (sur clinicalTrials) | |||
| IUCT ONCOPOLE - Hématologie - 31059 - Toulouse - France | Loïc YSEBAERT, Dr | Contact (sur clinicalTrials) | |||
| Vannes - Chba - Vannes - France | Antoine BONNET, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
- 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.
- 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