Clinical trial NCT02477696: Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)
Official title: A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase III Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Acerta Pharma BV
Sponsor class: INDUSTRY
First posted: 2015-06-23
Enrollment: 533
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.


Eligibility criteria: Inclusion Criteria:

* Men and women ≥ 18 years of age.
* ECOG performance status of 0 to 2.
* Diagnosis of CLL.
* Must have ≥ 1 of the following high-risk prognostic factors:

  * Presence of 17p del by central laboratory.
  * Presence of 11q del by central laboratory.
* Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment
* Must have received ≥ 1 prior therapies for CLL.
* Meet the following laboratory parameters:

  * Absolute neutrophil count (ANC) ≥ 750 cells/μL or ≥ 500 cells/μL in participants with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
  * Platelet count ≥ 30,000 cells/μL without transfusion support 7 days before assessment. Participants with transfusion-dependent thrombocytopenia are excluded.
  * Serum aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN).
  * Total bilirubin ≤ 1.5 x ULN.
  * Estimated creatinine clearance ≥ 30 mL/min.

Exclusion Criteria:

* Known CNS lymphoma or leukemia.
* Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
* Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
* Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor or a B-cell lymphoma-2 (BCL-2) inhibitor.
* Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
* Prior radio- or toxin-conjugated antibody therapy.
* Prior allogeneic stem cell or autologous transplant.
* Major surgery within 4 weeks before first dose of study drug.
* Prior malignancy, except for adequately treated lentigo maligna melanoma, non-melanomatous skin cancer, in situ cervical carcinoma or other malignancy treated with no evidence of active disease \> 3 years before Screening and at low risk for recurrence.
* Significant cardiovascular disease within 6 months of screening.
* Known history of infection with human immunodeficiency virus (HIV).
* History of stroke or intracranial hemorrhage within 6 months before randomization.
* History of bleeding diathesis.
* Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug.
* Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor/inducer.

Primary outcomes:
measure: Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment
timeFrame: Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Infections Grade >= 3
timeFrame: Day 1 through 83.5 months (maximum observed duration)
measure: Number of Participants With Treatment-emergent Richter's Transformation
timeFrame: Day 1 through 83.5 months (maximum observed duration)
measure: Number of Participants With Treatment-emergent Atrial Fibrillation
timeFrame: Day 1 through 83.5 months (maximum observed duration)
measure: Overall Survival (OS)
timeFrame: Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 83.5 months (maximum observed duration)
measure: Number of Participants With Treatment-emergent Laboratory Abnormalities
timeFrame: Day 1 through 83.5 months (maximum observed duration)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: Day 1 through 83.5 months (maximum observed duration)
measure: Percentage of Participants With Lymphocytosis
timeFrame: Day 1 through 83.5 months (maximum observed duration)
measure: Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline
timeFrame: Baseline (Days -28 to -1)
measure: Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Berkeley
country: United States
facility: Research Site
state: California
city: Duarte
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Palo Alto
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
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state: California
city: Jacksonville
country: United States
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state: Florida
city: Tampa
country: United States
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state: Florida
city: Athens
country: United States
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state: Georgia
city: Harvey
country: United States
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state: Illinois
city: Peoria
country: United States
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state: Illinois
city: Wichita
country: United States
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state: Kansas
city: Minneapolis
country: United States
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state: Minnesota
city: Rochester
country: United States
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state: Minnesota
city: Billings
country: United States
facility: Research Site
state: Montana
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Lake Success
country: United States
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state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
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state: New York
city: Durham
country: United States
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state: North Carolina
city: Columbus
country: United States
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state: Ohio
city: Philadelphia
country: United States
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state: Pennsylvania
city: Houston
country: United States
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state: Texas
city: Round Rock
country: United States
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state: Texas
city: Charlottesville
country: United States
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state: Virginia
city: Tacoma
country: United States
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state: Washington
city: Northwest WA
country: United States
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state: Wisconsin
city: Darlinghurst
country: Australia
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city: Frankston
country: Australia
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city: Melbourne
country: Australia
facility: Research Site
city: St Leonards
country: Australia
facility: Research Site
city: Waratah NSW
country: Australia
facility: Research Site
city: Wollongong
country: Australia
facility: Research Site
city: Brugge
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Ghent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Indgang 27B
country: Denmark
facility: Research Site
city: Bobigny
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Pierre-Benite
country: France
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city: Rennes Cedex
country: France
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city: Rouen
country: France
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city: Toulouse Cedex
country: France
facility: Research Site
city: München
country: Germany
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city: Ulm
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Kaposvár
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Petah Tikvah
country: Israel
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Tiberias
country: Israel
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Cagliari
country: Italy
facility: Research Site
city: Cona
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
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city: Modena
country: Italy
facility: Research Site
city: Ravenna
country: Italy
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city: Rome
country: Italy
facility: Research Site
city: Almere
country: Netherlands
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city: Amsterdam
country: Netherlands
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city: Blaricum
country: Netherlands
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city: Breda
country: Netherlands
facility: Research Site
city: Delft
country: Netherlands
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city: Dordrecht
country: Netherlands
facility: Research Site
city: Geleen
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Haarlem
country: Netherlands
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Zutphens
country: Netherlands
facility: Research Site
city: Addington
country: New Zealand
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Tauranga
country: New Zealand
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Opole
country: Poland
facility: Research Site
city: Slupsk
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Murcia
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Instabul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Bournemouth
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Greater London
country: United Kingdom
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
city: Surrey
country: United Kingdom
facility: Research Site
Study officials:
affiliation: 1-888-292-9613
name: Acerta Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.
citation: Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, O'Brien S, Yenerel MN, Illes A, Kay N, Garcia-Marco JA, Mato A, Pinilla-Ibarz J, Seymour JF, Lepretre S, Stilgenbauer S, Robak T, Rothbaum W, Izumi R, Hamdy A, Patel P, Higgins K, Sohoni S, Jurczak W. Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. J Clin Oncol. 2021 Nov 1;39(31):3441-3452. doi: 10.1200/JCO.21.01210. Epub 2021 Jul 26.