Ignite Creation Date:
2024-05-06 @ 4:23 PM
Last Modification Date:
2024-10-26 @ 2:09 PM
Study NCT ID:
NCT04963946
Status:
RECRUITING
Last Update Posted:
2024-06-20
First Post:
2021-07-06
Brief Title:
STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia
Sponsor:
French Innovative Leukemia Organisation
Organization:
French Innovative Leukemia Organisation
Study Overview
Official Title:
STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
STAIR
Brief Summary:
The irreversible Brutons Tyrosine Kinase BTK inhibitor acalabrutinib ACA has potent clinical activity as a single agent in patients with treatment naive and RelapsedRefractory 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
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 12 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 v5
MinimalMeasurable 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
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 12 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 v5
MinimalMeasurable 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None