Untreated Chronic Lymphocytic LeukemiaPhase 2STAIRNCT04963946
STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia
A Phase 2 study testing Stop ACA and ACA Continuation in people with Untreated Chronic Lymphocytic Leukemia, run by French Innovative Leukemia Organisation at 32 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Untreated Chronic Lymphocytic Leukemia
- What is being tested?
- Stop ACA and ACA Continuation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 32 sitesFrance
- Study dates
- 18 Oct 2021to 1 Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
France32 sites
Chu Angers
Angers, 49933
ARGENTEUIL - Centre hospitalier Victor Dupouy
Argenteuil
Ch Avignon
Avignon, 84000
Ch Cote Basque
Bayonne, 64109
BOBIGNY - Hôpital Avicenne
Bobigny
Hôpital Privé Sévigné
Cesson-Sévigné, 35510
CHU Estaing - Hématologie Clinique Adulte
Clermont-Ferrand, 63000
Corbeil-Essonnes -
Corbeil-Essonnes
CHU Grenoble - Hématologie
Grenoble, 388043
Centre Hospitalier du Mans
Le Mans, 72000
Hôpital Saint Vincent de Paul
Lille, 59000
Centre Léon Bérard - Hématologie
Lyon, 69373
Institut Paoli-Calmettes - Hématologie Clinique
Marseille, 13273
Centre Hospitalier Regional Metz Thionville
Metz, 57085
Hôpital Saint-Eloi - Hématologie Clinique
Montpellier, 34295
Hopital E.Muller
Mulhouse, 68100
CHR ORLEANS - Hématologie
Orléans, 44100
Hopital Pitie Salpetriere Service Hematologie Clinique - Pavillon de L'Enfant Et Adolescent
Paris, 75651
CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique
Perpignan, 66000
Bordeaux Pessac
Pessac, 33604
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire
Poitiers, 86021
CERGY-PONTOISE - Centre Hospitalier René Dubos
Pontoise
Chu Reims
Reims, 51092
CHU Pontchaillou - Hématologie Clinique BMT-HC
Rennes, 35033
Centre Henri Becquerel - Service Hématologie Clinique
Rouen, 76038
Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez, 42271
IUCT ONCOPOLE - Hématologie
Toulouse, 31059
Hôpital Bretonneau - Hématologie et Thérapie Cellulaire
Tours, 37044
CHU Nancy Brabois
Vandœuvre-lès-Nancy, 54500
Vannes - Chba
Vannes
VERSAILLES - Hôpital André Mignot
Versailles
About this study
Official title: STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia. A FILO Study.
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.
Read the detailed description
This multicenter, non comparative, randomized phase II trial aims at evaluating the impact of a stopping ACA strategy on PFS of CLL patients >70 years or with coexisting comorbidities.
Patients will receive continuous Acalabrutinib (ACA) at 100 mg bid for 18 months. Dose adaptations will be made according to labels.
In case of first occurrence of grade ≥3 non-hematological toxicity, febrile grade ≥3 neutropenia or grade ≥4 hematological toxicity treatment must be stopped until recovering grade 1 or baseline state.
- 1st and second occurrence : restart at 100 mg twice daily
- 3rd occurrence : restart at 100 mg once daily
- 4th occurrence : discontinue acalabrutinib
At month 19 day 1, patients will be randomized (1:2) in two arms:
- Arm 1 = Control arm (acalabrutinib) continuing acalabrutinib until disease progression or unacceptable toxicity or
- Arm 2 = Experimental arm (watch and monitor) without ACA (see trial design).
Upon progression in the experimental arm, all patients will be re-treated with ACA at the last received dose after central reviewing of treatment criteria.
Upon progression in the control arm, patients will receive next line therapy at the discretion of their physicians and according to iwCLL 2018 criteria.
Patients will be monitored every three months until M31 then every 6 months until M60 or progression for both response and toxicity according to CTCAE v.5.
Minimal/Measurable Residual Disease (MRD) assessment will be done at month 19 day 1 in the peripheral blood.
CT-scan will be performed at baseline, then at month 19 day 1 and every 6 months within the year after randomization.
- Conditions
- Untreated Chronic Lymphocytic Leukemia
- Being tested
- Stop ACA, ACA Continuation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stop ACADrug
discontinuation of acalabrutinib after 18 months in treatment-naïve CLL patients
ACA ContinuationDrug
continuation of acalabrutinib at the same dose
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: ACA Continuation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: until 12 months after acalabrutinib interruption
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2021
- Study start18 Oct 2021
- Primary completion1 Aug 2025
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Untreated Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- multicenter, non comparative, randomized, stop and restart
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- French Innovative Leukemia Organisation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Loïc Ysebaert, Pr, Principal investigator, French Innovative Leukemia OrganisationRomain GUIEZE, Pr, Principal investigator, French Innovative Leukemia Organisation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04963946
- Sponsor's protocol ID
- FILOCLL14 - STAIR
- Acronym
- STAIR
- Status last verified
- Nov 2025
- First submitted
- 6 Jul 2021
- Last updated
- 3 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia. A FILO Study.
- ClinicalTrials.gov ID
- NCT04963946
- Acronym / sponsor ID
- STAIR / FILOCLL14 - STAIR
- Conditions
- Untreated Chronic Lymphocytic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- French Innovative Leukemia OrganisationUniversity, hospital or other
- Study start
- 18 Oct 2021 (actual)
- Primary completion
- 1 Aug 2025 (actual)
- Study completion
- 1 Aug 2028 (estimated)
- First posted
- 15 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This multicenter, non comparative, randomized phase II trial aims at evaluating the impact of a stopping ACA strategy on PFS of CLL patients >70 years or with coexisting comorbidities.
Patients will receive continuous Acalabrutinib (ACA) at 100 mg bid for 18 months. Dose adaptations will be made according to labels.
In case of first occurrence of grade ≥3 non-hematological toxicity, febrile grade ≥3 neutropenia or grade ≥4 hematological toxicity treatment must be stopped until recovering grade 1 or baseline state.
- 1st and second occurrence : restart at 100 mg twice daily
- 3rd occurrence : restart at 100 mg once daily
- 4th occurrence : discontinue acalabrutinib
At month 19 day 1, patients will be randomized (1:2) in two arms:
- Arm 1 = Control arm (acalabrutinib) continuing acalabrutinib until disease progression or unacceptable toxicity or
- Arm 2 = Experimental arm (watch and monitor) without ACA (see trial design).
Upon progression in the experimental arm, all patients will be re-treated with ACA at the last received dose after central reviewing of treatment criteria.
Upon progression in the control arm, patients will receive next line therapy at the discretion of their physicians and according to iwCLL 2018 criteria.
Patients will be monitored every three months until M31 then every 6 months until M60 or progression for both response and toxicity according to CTCAE v.5.
Minimal/Measurable Residual Disease (MRD) assessment will be done at month 19 day 1 in the peripheral blood.
CT-scan will be performed at baseline, then at month 19 day 1 and every 6 months within the year after randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- multicenter, non comparative, randomized, stop and restart
| Arm | Type | Receives |
|---|---|---|
| watch and monitor | Experimental | Drug: Stop ACAAfter 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. |
| Acalabrutinib | Active comparator | Drug: ACA ContinuationAfter 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 |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (31 listed)
- Known HIV seropositivity
- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stop ACAdiscontinuation of acalabrutinib after 18 months in treatment-naïve CLL patients | Drug | watch and monitor |
| ACA Continuationcontinuation of acalabrutinib at the same dose | Drug | Acalabrutinib |
Primary outcome
Progression-free survival (PFS) at one year after acalabrutinib interruption
Time frame: until 12 months 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Individual participant dataSharing planned: No
Related trials for Untreated Chronic Lymphocytic Leukemia
Active, not recruitingPhase 3
Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia
Untreated Chronic Lymphocytic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Loïc Ysebaert, Pr principal investigator
French Innovative Leukemia Organisation
Romain GUIEZE, Pr principal investigator
French Innovative Leukemia Organisation
32 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stop ACA and ACA Continuation in people with Untreated Chronic Lymphocytic Leukemia, run by French Innovative Leukemia Organisation at 32 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) at one year after acalabrutinib interruption (time frame: until 12 months after acalabrutinib interruption). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025; AzTrials last refreshed its copy on 8 Nov 2026.