STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia (STAIR)
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|ClinicalTrials.gov Identifier: NCT04963946|
Recruitment Status : Recruiting
First Posted : July 15, 2021
Last Update Posted : February 23, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Untreated Chronic Lymphocytic Leukemia||Drug: Stop ACA Drug: ACA Continuation||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||160 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||multicenter, non comparative, randomized, stop and restart|
|Masking:||None (Open Label)|
|Official Title:||STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia|
|Actual Study Start Date :||October 18, 2021|
|Estimated Primary Completion Date :||April 15, 2024|
|Estimated Study Completion Date :||December 31, 2026|
Experimental: watch and monitor
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
discontinuation of acalabrutinib after 18 months in treatment-naïve CLL patients
Active Comparator: Acalabrutinib
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
continuation of acalabrutinib at the same dose
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04963946
|Contact: Delphine NOLLET||218370609 ext +email@example.com|
|Contact: Valérie ROUILLE, Pr||467332645 ext +firstname.lastname@example.org|
|Principal Investigator:||Loïc Ysebaert, Pr||French Innovative Leukemia Organisation|
|Principal Investigator:||Romain GUIEZE, Pr||French Innovative Leukemia Organisation|