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

NCT ID: NCT02477696

Last Updated: 2025-11-20

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

533 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-28

Study Completion Date

2028-01-03

Brief Summary

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

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Acalabrutinib

Intervention Type DRUG

Participants will receive oral acalabrutinib as stated in arm description.

Ibrutinib

Participants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first.

Group Type ACTIVE_COMPARATOR

Ibrutinib

Intervention Type DRUG

Participants will receive oral ibrutinib as stated in arm description.

Interventions

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Acalabrutinib

Participants will receive oral acalabrutinib as stated in arm description.

Intervention Type DRUG

Ibrutinib

Participants will receive oral ibrutinib as stated in arm description.

Intervention Type DRUG

Other Intervention Names

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ACP-196

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Acerta Pharma BV

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Acerta Clinical Trials

Role: STUDY_DIRECTOR

1-888-292-9613

Locations

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Phoenix, Arizona, United States

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Anaheim, California, United States

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Berkeley, California, United States

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Duarte, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Palo Alto, California, United States

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Santa Rosa, California, United States

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Jacksonville, Florida, United States

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Tampa, Florida, United States

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Athens, Georgia, United States

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Harvey, Illinois, United States

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Peoria, Illinois, United States

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Wichita, Kansas, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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Billings, Montana, United States

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Hackensack, New Jersey, United States

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Lake Success, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Columbus, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Houston, Texas, United States

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Round Rock, Texas, United States

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Charlottesville, Virginia, United States

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Tacoma, Washington, United States

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Northwest WA, Wisconsin, United States

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Darlinghurst, , Australia

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Frankston, , Australia

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Melbourne, , Australia

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St Leonards, , Australia

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Waratah NSW, , Australia

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Wollongong, , Australia

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Bruges, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Yvoir, , Belgium

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Aalborg, , Denmark

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Indgang 27B, , Denmark

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Bobigny, , France

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Créteil, , France

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Pierre-Bénite, , France

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Rennes, , France

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Rouen, , France

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Toulouse, , France

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München, , Germany

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Ulm, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Kaposvár, , Hungary

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Haifa, , Israel

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Haifa, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Nahariya, , Israel

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Petah Tikvah, , Israel

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Tel Litwinsky, , Israel

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Tiberias, , Israel

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Bologna, , Italy

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Cagliari, , Italy

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Cona, , Italy

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Florence, , Italy

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Meldola, , Italy

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Ravenna, , Italy

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Rome, , Italy

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Almere Stad, , Netherlands

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Amsterdam, , Netherlands

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Blaricum, , Netherlands

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Breda, , Netherlands

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Delft, , Netherlands

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Dordrecht, , Netherlands

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Geleen, , Netherlands

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Groningen, , Netherlands

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Haarlem, , Netherlands

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Leiden, , Netherlands

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Rotterdam, , Netherlands

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Rotterdam, , Netherlands

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Utrecht, , Netherlands

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Zutphens, , Netherlands

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Addington, , New Zealand

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Auckland, , New Zealand

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Tauranga, , New Zealand

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Gdynia, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Olsztyn, , Poland

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Opole, , Poland

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Słupsk, , Poland

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Wroclaw, , Poland

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Murcia, , Spain

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Santander, , Spain

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Instabul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Bournemouth, , United Kingdom

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Cambridge, , United Kingdom

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Cardiff, , United Kingdom

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Greater London, , United Kingdom

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Hull, , United Kingdom

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Leeds, , United Kingdom

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Leicester, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Nottingham, , United Kingdom

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Plymouth, , United Kingdom

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Southampton, , United Kingdom

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Surrey, , United Kingdom

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Countries

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United States Australia Belgium Denmark France Germany Hungary Israel Italy Netherlands New Zealand Poland Spain Turkey (Türkiye) United Kingdom

References

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Byrd JC, Hakre S, Ghia P. How well does acalabrutinib work and how safe is it to treat patients with chronic lymphocytic leukemia/small lymphocytic lymphoma who have had previous treatments? a plain language summary of 2 key studies. Future Oncol. 2025 Nov;21(26):3343-3357. doi: 10.1080/14796694.2025.2494976. Epub 2025 Jun 8.

Reference Type DERIVED
PMID: 40485230 (View on PubMed)

Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.

Reference Type DERIVED
PMID: 39563886 (View on PubMed)

Woyach JA, Jones D, Jurczak W, Robak T, Illes A, Kater AP, Ghia P, Byrd JC, Seymour JF, Long S, Mohamed N, Benrashid S, Lai TH, De Jesus G, Lai R, de Bruin G, Rule S, Munugalavadla V. Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib. Blood. 2024 Sep 5;144(10):1061-1068. doi: 10.1182/blood.2023023659.

Reference Type DERIVED
PMID: 38754046 (View on PubMed)

Seymour JF, Byrd JC, Ghia P, Kater AP, Chanan-Khan A, Furman RR, O'Brien S, Brown JR, Munir T, Mato A, Stilgenbauer S, Bajwa N, Miranda P, Higgins K, John E, de Borja M, Jurczak W, Woyach JA. Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial. Blood. 2023 Aug 24;142(8):687-699. doi: 10.1182/blood.2022018818.

Reference Type DERIVED
PMID: 37390310 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34398557 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34310172 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2023-509347-27-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-005530-64

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACE-CL-006

Identifier Type: -

Identifier Source: org_study_id

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