This study has been transitioned to CTIS with ID 2023-509349-11-00 check the CTIS register for the current data. Primary objective: To determine the efficacy of the combination of acalabrutinib and venetoclax without obinutuzumab (AV; Arm A), or…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the efficacy of AV (Arm A) compared with chemoimmunotherapy
(FCR/BR; Arm C) on the basis of the following endpoint:
- PFS after randomization, defined as the time from randomization to the first
occurrence of disease progression or death from any cause (whichever occurs
first), as determined by the Independent Review Committee (IRC) according to
the IWCLL 2018 criteria
Secondary outcome
To evaluate the efficacy of AVG (Arm B) versus FCR/BR (Arm C) based on the
following endpoint:
- PFS after randomization, defined as the time from randomization to the first
occurrence of disease progression or death from any cause (whichever
occurs first), as determined by the IRC assessment according to the IWCLL 2018
criteria
Background summary
This randomized, global, multicenter, open-label, Phase 3 study will evaluate
the efficacy and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in
subjects with previously untreated CLL without del(17p) or TP53. Subjects will
be randomized in a 1:1:1 ratio into 3 arms through a block stratified
randomization procedure.
Study objective
This study has been transitioned to CTIS with ID 2023-509349-11-00 check the CTIS register for the current data.
Primary objective: To determine the efficacy of the combination of
acalabrutinib and venetoclax without obinutuzumab (AV; Arm A), or with
obinutuzumab (AVG; Arm B) compared with chemoimmunotherapy
(fludarabine/cyclophosphamide/rituximab [FCR]/bendamustine/rituximab [BR]; Arm
C) by assessment of PFS (progression-free survival) in patients with previously
untreated Chronic Lymphocytic Leukemia without del(17p) or tp53 mutation.
Study design
Randomized, Phase Ill, open-label study. Randomisation 1:1:1 to:
- Acalabrutinib and venetoclax
- Acalabrutinib, venetoclax and obinutuzumab
- Chemoimmunotherapy; fludarabine/cyclophosphamide/rituximab (FCR) or
bendamustine/rituximab (BR) (investigator*s choice).
Approximately 780 subjects will receive treatment for a set period of time.
The study includes screening (30 days), treatment (from randomization until
study drug discontinuation) and follow-up phase.
Intervention
- Acalabrutinib (Calquence)
- Venetoclax (Venclyxto)
- Obinutuzumab (Gazyvaro)
- Chemoimmunotherapy: fludarabine/cyclophosphamide/rituximab (FCR),
bendamustine/rituximab (BR)
Study burden and risks
Patients in arm A and B will visit the hospital more often compared to standard
of care. During the study visit additional blood, CT scans and bone marrow
aspirate/biopsies will be taken compared to standard of care. The patients are
also asked to complete questionnaires and diaries and to provide an optional
sputum sample.
The study drugs may reduce the CLL, but this is not sure. The study drugs may
cause side effects.
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
- Men and women >=18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Diagnosis of CLL and active disease requiring treatment per iwCLL 2018
criteria
- *Adequate bone marrow function within 1 week of Screening
o ANC >=750 cells/ µL (0.75x10^9 /L); ANC >=500 µL (0.50x10^9 /L) in
subjects with documented bone marrow involvement of CLL
o Platelet count >=50,000 cells/ µL (50x10^9 /L); platelet count >=30,000 µL
(30x10^9 /L) in subjects with documented bone marrow involvement of CLL
- Serum AST and ALT <=2.5xULN
- Total bilirubin <=2xULN
- Estimated creatinine clearance of >=50 mL/min; >=70 mL/min for FCR (Arm C)
Exclusion criteria
- Any prior CLL-specific therapies.
- Detected del(17p) or TP53 mutation.
- Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g.,
Richter's transformation, prolymphocytic leukemia [PLL], or diffuse large B
cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia.
- History of confirmed progressive multifocal leukoencephalopathy (PML).
- Major surgical procedure within 30 days before the first dose of study drug.
- 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. Note: Subjects with controlled,
asymptomatic atrial fibrillation are allowed to enroll on study.
- History of stroke or intracranial hemorrhage within 6 months before first
dose of study drug.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-509349-11-00 |
| EudraCT | EUCTR2018-002443-28-NL |
| ClinicalTrials.gov | NCT03836261 |
| CCMO | NL70443.018.19 |