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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03836261




Registration number
NCT03836261
Ethics application status
Date submitted
6/02/2019
Date registered
11/02/2019
Date last updated
1/10/2024

Titles & IDs
Public title
Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
Scientific title
A Randomized, Multicenter, Open-Label, Phase 3 Study to Compare the Efficacy and Safety of Acalabrutinib (ACP-196) in Combination With Venetoclax With and Without Obinutuzumab Compared to Investigator's Choice of Chemoimmunotherapy in Subjects With Previously Untreated Chronic Lymphocytic Leukemia Without Del(17p) or TP53 Mutation (AMPLIFY)
Secondary ID [1] 0 0
D8221C00001
Secondary ID [2] 0 0
ACE-CL-311
Universal Trial Number (UTN)
Trial acronym
AMPLIFY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Acalabrutinib
Treatment: Drugs - Venetoclax
Treatment: Drugs - Chemoimmunotherapy
Treatment: Drugs - Obinutuzumab

Experimental: Acalabrutinib, Venetoclax - Acalabrutinib in combination with Venetoclax

Experimental: Acalabrutinib, Venetoclax, Obinutuzumab - Acalabrutinib in combination with Venetoclax with Obinutuzumab

Active comparator: Chemoimmunotherapy - Chemoimmunotherapy

FCR: Fludarabine, Cyclophosphamide and Rituximab

BR: Bendamustine and Rituximab


Treatment: Drugs: Acalabrutinib
Acalabrutinib,

Treatment: Drugs: Venetoclax
Venetoclax

Treatment: Drugs: Chemoimmunotherapy
fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)

Treatment: Drugs: Obinutuzumab
Obinutuzumab
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS
Timepoint [1] 0 0
6 years
Secondary outcome [1] 0 0
To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS
Timepoint [1] 0 0
6 years
Secondary outcome [2] 0 0
To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared with FCR or BR (Arm C): PFS defined the same as above per investigator assessment.
Timepoint [2] 0 0
6 years

Eligibility
Key inclusion criteria
* Men and women =18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018)
* Active disease per IWCLL 2018 criteria that requires treatment.
* Participants must use highly effective birth control throughout the study.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).
* Received any investigational drug within 30 days before first dose of study drug.
* 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.
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
* Received a live virus vaccination within 28 days of first dose of study drug.
* Known history of infection with human immunodeficiency virus (HIV).
* Serologic status reflecting active hepatitis B or C infection.
* History of known hypersensitivity or anaphylactic reactions to study drugs or excipients.
* History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
* Known bleeding disorders.
* Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
* Female participants must not be breastfeeding or pregnant.
* Concurrent participation in another therapeutic clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2027
Actual
Sample size
Target
Accrual to date
Final
984
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Darlinghurst
Recruitment hospital [3] 0 0
Research Site - Heidelberg
Recruitment hospital [4] 0 0
Research Site - Kogarah
Recruitment hospital [5] 0 0
Research Site - Melbourne
Recruitment hospital [6] 0 0
Research Site - Nedlands
Recruitment hospital [7] 0 0
Research Site - Waratah
Recruitment hospital [8] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
2298 - Waratah
Recruitment postcode(s) [8] 0 0
4102 - Woolloongabba
Recruitment outside Australia
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California
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Uppsala
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Örebro
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Taiwan
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Kaohsiung
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Taichung
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Taiwan
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Taoyuan City
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Turkey
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Ankara
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Izmir
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Kurupelit
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Talas
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United Kingdom
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Cambridge
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United Kingdom
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Canterbury
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United Kingdom
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Acerta Pharma BV
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL
Trial website
https://clinicaltrials.gov/study/NCT03836261
Trial related presentations / publications
Davids MS, Lampson BL, Tyekucheva S, Wang Z, Lowney JC, Pazienza S, Montegaard J, Patterson V, Weinstock M, Crombie JL, Ng SY, Kim AI, Jacobson CA, LaCasce AS, Armand P, Arnason JE, Fisher DC, Brown JR. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1391-1402. doi: 10.1016/S1470-2045(21)00455-1. Epub 2021 Sep 14.
Gordon MJ, Danilov AV. The evolving role of Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia. Ther Adv Hematol. 2021 Jan 30;12:2040620721989588. doi: 10.1177/2040620721989588. eCollection 2021.
Public notes

Contacts
Principal investigator
Name 0 0
Jennifer Brown
Address 0 0
Dana Farber Mass General Brigham Cancer Care Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03836261