Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)
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
3 other identifiers
interventional
533
15 countries
130
Brief Summary
This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2015
Longer than P75 for phase_3
130 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 12, 2015
CompletedFirst Posted
Study publicly available on registry
June 23, 2015
CompletedStudy Start
First participant enrolled
July 28, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 15, 2020
CompletedResults Posted
Study results publicly available
January 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
January 3, 2028
ExpectedMarch 27, 2026
March 1, 2026
5.1 years
June 12, 2015
September 10, 2021
March 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment
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 Outcomes (10)
Number of Participants With Treatment-emergent Infections Grade >= 3
Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Richter's Transformation
Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Atrial Fibrillation
Day 1 through 83.5 months (maximum observed duration)
Overall Survival (OS)
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)
Day 1 through 83.5 months (maximum observed duration)
- +5 more secondary outcomes
Study Arms (2)
Acalabrutinib
EXPERIMENTALParticipants will receive oral acalabrutinib 100 mg twice daily (BID) until disease progression (PD), or unacceptable toxicity, or other reasons for discontinuation, whichever occurs first.
Ibrutinib
ACTIVE COMPARATORParticipants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first.
Interventions
Participants will receive oral acalabrutinib as stated in arm description.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Acerta Pharma BVlead
Study Sites (130)
Research Site
Phoenix, Arizona, 85054, United States
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Anaheim, California, 92801, United States
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Berkeley, California, 94704, United States
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Duarte, California, 91010, United States
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La Jolla, California, 92093, United States
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Los Angeles, California, 90095, United States
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Palo Alto, California, 94304, United States
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Santa Rosa, California, 95403, United States
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Jacksonville, Florida, 32224, United States
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Tampa, Florida, 33612, United States
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Athens, Georgia, 30607, United States
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Harvey, Illinois, 60426, United States
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Peoria, Illinois, 61615, United States
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Wichita, Kansas, 67214, United States
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Minneapolis, Minnesota, 55426, United States
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Rochester, Minnesota, 55905, United States
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Billings, Montana, 59102, United States
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Hackensack, New Jersey, ?07601, United States
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Lake Success, New York, 11042, United States
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New Hyde Park, New York, 11042, United States
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New York, New York, 10021, United States
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New York, New York, 10029, United States
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New York, New York, 10065, United States
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Durham, North Carolina, 27710, United States
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Columbus, Ohio, 43210, United States
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Philadelphia, Pennsylvania, 19104, United States
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Houston, Texas, 77030, United States
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Round Rock, Texas, 78665, United States
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Charlottesville, Virginia, 22908, United States
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Tacoma, Washington, 98405, United States
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Northwest WA, Wisconsin, 20007, United States
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Darlinghurst, 2010, Australia
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Frankston, 3199, Australia
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Melbourne, 3000, Australia
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St Leonards, 2065, Australia
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Waratah NSW, 2298, Australia
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Wollongong, 2500, Australia
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Bruges, 8000, Belgium
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Brussels, 1200, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Yvoir, 5530, Belgium
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Aalborg, 9100, Denmark
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Indgang 27B, DK-4000, Denmark
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Bobigny, 93000, France
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Créteil, 94010, France
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Pierre-Bénite, 69310, France
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Rennes, 35000, France
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Rouen, 76038, France
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Toulouse, 31059, France
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München, 81241, Germany
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Ulm, 89081, Germany
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Budapest, 1083, Hungary
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Budapest, 1122, Hungary
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Debrecen, 4032, Hungary
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Kaposvár, 7400, Hungary
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Haifa, 31000, Israel
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Haifa, 31096, Israel
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Haifa, 34362, Israel
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Jerusalem, 9103102, Israel
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Nahariya, 22100, Israel
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Petah Tikvah, 49102, Israel
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Tel Litwinsky, 52621, Israel
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Tiberias, 15208, Israel
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Bologna, 40138, Italy
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Cagliari, 9121, Italy
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Cona, 44124, Italy
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Florence, 50134, Italy
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Milan, 20162, Italy
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Modena, 41100, Italy
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Ravenna, 48121, Italy
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Rome, 168, Italy
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Almere Stad, 1315 RA, Netherlands
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Amsterdam, 1105 AZ, Netherlands
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Blaricum, 1261, Netherlands
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Breda, 4818 CK, Netherlands
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Delft, 2600 GA, Netherlands
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Dordrecht, 3317, Netherlands
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Geleen, 6162 BG, Netherlands
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Groningen, 9700, Netherlands
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Haarlem, 2035 RC, Netherlands
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Leiden, 2333, Netherlands
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Rotterdam, 3062 PA, Netherlands
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Rotterdam, 3083 AN, Netherlands
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Utrecht, 3584, Netherlands
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Zutphens, 7207 AE, Netherlands
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Addington, 8011, New Zealand
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Auckland, ?0620, New Zealand
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Tauranga, 3112, New Zealand
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Bydgoszcz, 85-168, Poland
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Gdansk, 80-129, Poland
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Gdynia, 81-519, Poland
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Krakow, 30-727, Poland
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Lodz, 93-510, Poland
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Olsztyn, 10-228, Poland
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Opole, 46-020, Poland
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Słupsk, 76-200, Poland
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Wroclaw, 50-001, Poland
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Barcelona, 8907, Spain
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Barcelona, ?08041, Spain
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Madrid, 28006, Spain
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Madrid, 28009, Spain
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Madrid, 28031, Spain
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Madrid, 28041, Spain
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Majadahonda, 28222, Spain
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Murcia, 30008, Spain
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Santander, 39008, Spain
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Ankara, 6230, Turkey (Türkiye)
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Ankara, 6560, Turkey (Türkiye)
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Instabul, 34365, Turkey (Türkiye)
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Izmir, 35040, Turkey (Türkiye)
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Izmir, 35340, Turkey (Türkiye)
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Kayseri, 38030, Turkey (Türkiye)
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Birmingham, B9 5SS, United Kingdom
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Bournemouth, BH7 7DW, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Cardiff, CF14 4XW, United Kingdom
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Greater London, E1 2AD, United Kingdom
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Hull, HU32JZ, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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Leicester, LE1 7RH, United Kingdom
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Liverpool, L7 8XP, United Kingdom
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London, SE5 9RS, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Nottingham, NG5 1PB, United Kingdom
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Plymouth, PL6 8DH, United Kingdom
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Southampton, SO16 6YD, United Kingdom
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Surrey, SM2 5PT, United Kingdom
Related Publications (6)
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.
PMID: 40485230DERIVEDAlfaifi 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.
PMID: 39563886DERIVEDWoyach 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.
PMID: 38754046DERIVEDSeymour 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.
PMID: 37390310DERIVEDKipps 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.
PMID: 34398557DERIVEDByrd 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.
PMID: 34310172DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- Acerta Pharma BV
Study Officials
- STUDY DIRECTOR
Acerta Clinical Trials
1-888-292-9613
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 12, 2015
First Posted
June 23, 2015
Study Start
July 28, 2015
Primary Completion
September 15, 2020
Study Completion (Estimated)
January 3, 2028
Last Updated
March 27, 2026
Results First Posted
January 28, 2022
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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.
- 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.
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.