Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)

May 22, 2026 updated by: Acerta Pharma BV

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

533

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Darlinghurst, Australia, 2010
        • Research Site
      • Frankston, Australia, 3199
        • Research Site
      • Melbourne, Australia, 3000
        • Research Site
      • St Leonards, Australia, 2065
        • Research Site
      • Waratah NSW, Australia, 2298
        • Research Site
      • Wollongong, Australia, 2500
        • Research Site
  • Belgium
      • Bruges, Belgium, 8000
        • Research Site
      • Brussels, Belgium, 1200
        • Research Site
      • Ghent, Belgium, 9000
        • Research Site
      • Leuven, Belgium, 3000
        • Research Site
      • Yvoir, Belgium, 5530
        • Research Site
  • Denmark
      • Aalborg, Denmark, 9100
        • Research Site
      • Indgang 27B, Denmark, DK-4000
        • Research Site
  • France
      • Bobigny, France, 93000
        • Research Site
      • Créteil, France, 94010
        • Research Site
      • Pierre-Bénite, France, 69310
        • Research Site
      • Rennes, France, 35000
        • Research Site
      • Rouen, France, 76038
        • Research Site
      • Toulouse, France, 31059
        • Research Site
  • Germany
      • München, Germany, 81241
        • Research Site
      • Ulm, Germany, 89081
        • Research Site
  • Hungary
      • Budapest, Hungary, 1083
        • Research Site
      • Budapest, Hungary, 1122
        • Research Site
      • Debrecen, Hungary, 4032
        • Research Site
      • Kaposvár, Hungary, 7400
        • Research Site
  • Israel
      • Haifa, Israel, 34362
        • Research Site
      • Haifa, Israel, 31096
        • Research Site
      • Haifa, Israel, 31000
        • Research Site
      • Jerusalem, Israel, 9103102
        • Research Site
      • Nahariya, Israel, 22100
        • Research Site
      • Petah Tikvah, Israel, 49102
        • Research Site
      • Tel Litwinsky, Israel, 52621
        • Research Site
      • Tiberias, Israel, 15208
        • Research Site
  • Italy
      • Bologna, Italy, 40138
        • Research Site
      • Cagliari, Italy, 9121
        • Research Site
      • Cona, Italy, 44124
        • Research Site
      • Florence, Italy, 50134
        • Research Site
      • Meldola, Italy, 47014
        • Research Site
      • Milan, Italy, 20162
        • Research Site
      • Milan, Italy, 20132
        • Research Site
      • Modena, Italy, 41100
        • Research Site
      • Ravenna, Italy, 48121
        • Research Site
      • Rome, Italy, 168
        • Research Site
  • Netherlands
      • Almere Stad, Netherlands, 1315 RA
        • Research Site
      • Amsterdam, Netherlands, 1105 AZ
        • Research Site
      • Blaricum, Netherlands, 1261
        • Research Site
      • Breda, Netherlands, 4818 CK
        • Research Site
      • Delft, Netherlands, 2600 GA
        • Research Site
      • Dordrecht, Netherlands, 3317
        • Research Site
      • Geleen, Netherlands, 6162 BG
        • Research Site
      • Groningen, Netherlands, 9700
        • Research Site
      • Haarlem, Netherlands, 2035 RC
        • Research Site
      • Leiden, Netherlands, 2333
        • Research Site
      • Rotterdam, Netherlands, 3062 PA
        • Research Site
      • Rotterdam, Netherlands, 3083 AN
        • Research Site
      • Utrecht, Netherlands, 3584
        • Research Site
      • Zutphens, Netherlands, 7207 AE
        • Research Site
  • New Zealand
      • Addington, New Zealand, 8011
        • Research Site
      • Auckland, New Zealand, ?0620
        • Research Site
      • Tauranga, New Zealand, 3112
        • Research Site
  • Poland
      • Bydgoszcz, Poland, 85-168
        • Research Site
      • Gdansk, Poland, 80-129
        • Research Site
      • Gdynia, Poland, 81-519
        • Research Site
      • Krakow, Poland, 30-727
        • Research Site
      • Lodz, Poland, 93-510
        • Research Site
      • Olsztyn, Poland, 10-228
        • Research Site
      • Opole, Poland, 46-020
        • Research Site
      • Słupsk, Poland, 76-200
        • Research Site
      • Wroclaw, Poland, 50-001
        • Research Site
  • Spain
      • Barcelona, Spain, 8907
        • Research Site
      • Barcelona, Spain, ?08041
        • Research Site
      • Madrid, Spain, 28031
        • Research Site
      • Madrid, Spain, 28041
        • Research Site
      • Madrid, Spain, 28009
        • Research Site
      • Madrid, Spain, 28006
        • Research Site
      • Majadahonda, Spain, 28222
        • Research Site
      • Murcia, Spain, 30008
        • Research Site
      • Santander, Spain, 39008
        • Research Site
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 6230
        • Research Site
      • Ankara, Turkey (Türkiye), 6560
        • Research Site
      • Instabul, Turkey (Türkiye), 34365
        • Research Site
      • Izmir, Turkey (Türkiye), 35340
        • Research Site
      • Izmir, Turkey (Türkiye), 35040
        • Research Site
      • Kayseri, Turkey (Türkiye), 38030
        • Research Site
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • Research Site
      • Bournemouth, United Kingdom, BH7 7DW
        • Research Site
      • Cambridge, United Kingdom, CB2 0QQ
        • Research Site
      • Cardiff, United Kingdom, CF14 4XW
        • Research Site
      • Greater London, United Kingdom, E1 2AD
        • Research Site
      • Hull, United Kingdom, HU32JZ
        • Research Site
      • Leeds, United Kingdom, LS9 7TF
        • Research Site
      • Leicester, United Kingdom, LE1 7RH
        • Research Site
      • Liverpool, United Kingdom, L7 8XP
        • Research Site
      • London, United Kingdom, SE5 9RS
        • Research Site
      • Manchester, United Kingdom, M20 4BX
        • Research Site
      • Nottingham, United Kingdom, NG5 1PB
        • Research Site
      • Plymouth, United Kingdom, PL6 8DH
        • Research Site
      • Southampton, United Kingdom, SO16 6YD
        • Research Site
      • Surrey, United Kingdom, SM2 5PT
        • Research Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Research Site
    • California
      • Anaheim, California, United States, 92801
        • Research Site
      • Berkeley, California, United States, 94704
        • Research Site
      • Duarte, California, United States, 91010
        • Research Site
      • La Jolla, California, United States, 92093
        • Research Site
      • Los Angeles, California, United States, 90095
        • Research Site
      • Palo Alto, California, United States, 94304
        • Research Site
      • Santa Rosa, California, United States, 95403
        • Research Site
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Research Site
      • Tampa, Florida, United States, 33612
        • Research Site
    • Georgia
      • Athens, Georgia, United States, 30607
        • Research Site
    • Illinois
      • Harvey, Illinois, United States, 60426
        • Research Site
      • Peoria, Illinois, United States, 61615
        • Research Site
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Research Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55426
        • Research Site
      • Rochester, Minnesota, United States, 55905
        • Research Site
    • Montana
      • Billings, Montana, United States, 59102
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, United States, ?07601
        • Research Site
    • New York
      • Lake Success, New York, United States, 11042
        • Research Site
      • New Hyde Park, New York, United States, 11042
        • Research Site
      • New York, New York, United States, 10021
        • Research Site
      • New York, New York, United States, 10065
        • Research Site
      • New York, New York, United States, 10029
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site
      • Round Rock, Texas, United States, 78665
        • Research Site
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Research Site
    • Washington
      • Tacoma, Washington, United States, 98405
        • Research Site
    • Wisconsin
      • Northwest WA, Wisconsin, United States, 20007
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acalabrutinib
Participants will receive oral acalabrutinib 100 mg twice daily (BID) until disease progression (PD), or unacceptable toxicity, or other reasons for discontinuation, whichever occurs first.
Drug: Acalabrutinib
Participants will receive oral acalabrutinib as stated in arm description.
Other Names:
  • ACP-196
Active Comparator: Ibrutinib
Participants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first.
Drug: Ibrutinib
Participants will receive oral ibrutinib as stated in arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment
Time Frame: Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)
The PFS is defined as the time from date of randomization to the date of first IRC-assessed PD or death due to any cause, whichever occurred first. PD (per International Workshop on Chronic Lymphocytic Leukemia [iwCLL] 2008 criteria): Lymphocytes >= 50% increase over baseline, or >= 50% increase in lymphadenopathy/hepatomegaly/splenomegaly, or >= 50% platelets or > 2 g/dL hemoglobin decreases from baseline secondary to chronic lymphocytic leukemia (CLL). The PFS is assessed using the Kaplan-Meier method.
Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Infections Grade >= 3
Time Frame: Day 1 through 83.5 months (maximum observed duration)
Number of participants with treatment-emergent infections Grade >=3 are reported.
Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Richter's Transformation
Time Frame: Day 1 through 83.5 months (maximum observed duration)
Richter's transformation is defined as the occurrence of an aggressive lymphoma in participants with a previous or concomitant diagnosis of CLL. Richter's transformation was assessed by central pathology. Number of participants with treatment-emergent Richter's transformation are reported.
Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Atrial Fibrillation
Time Frame: Day 1 through 83.5 months (maximum observed duration)
Number of participants with treatment-emergent atrial fibrillation (including atrial flutter) are reported.
Day 1 through 83.5 months (maximum observed duration)
Overall Survival (OS)
Time Frame: Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)
The OS is defined as the time from date of randomization to date of death due to any cause. The OS is assessed using the Kaplan-Meier method.
Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time Frame: Day 1 through 83.5 months (maximum observed duration)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Laboratory Abnormalities
Time Frame: Day 1 through 83.5 months (maximum observed duration)
Number of participants with treatment-emergent laboratory abnormalities are reported. Laboratory abnormality is defined as any abnormal finding during analysis of hematology and serum chemistry.
Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Time Frame: Day 1 through 83.5 months (maximum observed duration)
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, heart rate, and respiratory rate).
Day 1 through 83.5 months (maximum observed duration)
Percentage of Participants With Lymphocytosis
Time Frame: Day 1 through 83.5 months (maximum observed duration)
Percentage of participants with at least one occurrence of treatment-related lymphocytosis defined as an elevation in ALC of >= 50% compared with baseline and a postbaseline assessment of > 5000/μL in the peripheral blood are reported.
Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline
Time Frame: Baseline (Days -28 to -1)
Number of participants with ECG abnormality at baseline are reported.
Baseline (Days -28 to -1)
Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame: Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)
The ECOG performance status assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=death. Number of participants with shift from baseline (Days -28 to -1) to worst Grade 3 and 4 in ECOG performance status are reported.
Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Acerta Pharma BV

Investigators

  • Study Director: Acerta Clinical Trials, 1-888-292-9613

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2015

Primary Completion (Actual)

September 15, 2020

Study Completion (Estimated)

January 3, 2028

Study Registration Dates

First Submitted

June 12, 2015

First Submitted That Met QC Criteria

June 22, 2015

First Posted (Estimated)

June 23, 2015

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 22, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACE-CL-006
  • 2014-005530-64 (EudraCT Number)
  • 2023-509347-27-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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