Chronic Lymphocytic LeukemiaPhase 3NCT02477696
Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)
A Phase 3 study testing Acalabrutinib and Ibrutinib in people with Chronic Lymphocytic Leukemia, run by Acerta Pharma BV at 130 sites in 15 countries.
Trial summary
This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Acalabrutinib and Ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 533 participants
- Where
- 130 sitesin 15 countries
- Study dates
- 28 Jul 2015to 3 Jan 2028
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
130 sites in 15 countries.
130 sites in 15 countries
United States31 sites
Research Site
Anaheim, California, 92801
Research Site
Athens, Georgia, 30607
Research Site
Berkeley, California, 94704
Research Site
Billings, Montana, 59102
Research Site
Charlottesville, Virginia, 22908
Research Site
Columbus, Ohio, 43210
Research Site
Duarte, California, 91010
Research Site
Durham, North Carolina, 27710
Research Site
Hackensack, New Jersey, ?07601
Research Site
Harvey, Illinois, 60426
Research Site
Houston, Texas, 77030
Research Site
Jacksonville, Florida, 32224
Research Site
La Jolla, California, 92093
Research Site
Lake Success, New York, 11042
Research Site
Los Angeles, California, 90095
Research Site
Minneapolis, Minnesota, 55426
Research Site
New Hyde Park, New York, 11042
Research Site
New York, New York, 10021
Research Site
New York, New York, 10029
Research Site
New York, New York, 10065
Research Site
Northwest WA, Wisconsin, 20007
Research Site
Palo Alto, California, 94304
Research Site
Peoria, Illinois, 61615
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Phoenix, Arizona, 85054
Research Site
Rochester, Minnesota, 55905
Research Site
Round Rock, Texas, 78665
Research Site
Santa Rosa, California, 95403
Research Site
Tacoma, Washington, 98405
Research Site
Tampa, Florida, 33612
Research Site
Wichita, Kansas, 67214
United Kingdom15 sites
Research Site
Birmingham, B9 5SS
Research Site
Bournemouth, BH7 7DW
Research Site
Cambridge, CB2 0QQ
Research Site
Cardiff, CF14 4XW
Research Site
Greater London, E1 2AD
Research Site
Hull, HU32JZ
Research Site
Leeds, LS9 7TF
Research Site
Leicester, LE1 7RH
Research Site
Liverpool, L7 8XP
Research Site
London, SE5 9RS
Research Site
Manchester, M20 4BX
Research Site
Nottingham, NG5 1PB
Research Site
Plymouth, PL6 8DH
Research Site
Southampton, SO16 6YD
Research Site
Surrey, SM2 5PT
Netherlands14 sites
Research Site
Almere Stad, 1315 RA
Research Site
Amsterdam, 1105 AZ
Research Site
Blaricum, 1261
Research Site
Breda, 4818 CK
Research Site
Delft, 2600 GA
Research Site
Dordrecht, 3317
Research Site
Geleen, 6162 BG
Research Site
Groningen, 9700
Research Site
Haarlem, 2035 RC
Research Site
Leiden, 2333
Research Site
Rotterdam, 3062 PA
Research Site
Rotterdam, 3083 AN
Research Site
Utrecht, 3584
Research Site
Zutphens, 7207 AE
Italy10 sites
Research Site
Bologna, 40138
Research Site
Cagliari, 9121
Research Site
Cona, 44124
Research Site
Florence, 50134
Research Site
Meldola, 47014
Research Site
Milan, 20132
Research Site
Milan, 20162
Research Site
Modena, 41100
Research Site
Ravenna, 48121
Research Site
Rome, 168
Poland9 sites
Research Site
Bydgoszcz, 85-168
Research Site
Gdansk, 80-129
Research Site
Gdynia, 81-519
Research Site
Krakow, 30-727
Research Site
Lodz, 93-510
Research Site
Olsztyn, 10-228
Research Site
Opole, 46-020
Research Site
Słupsk, 76-200
Research Site
Wroclaw, 50-001
Spain9 sites
Research Site
Barcelona, 8907
Research Site
Barcelona, ?08041
Research Site
Madrid, 28006
Research Site
Madrid, 28009
Research Site
Madrid, 28031
Research Site
Madrid, 28041
Research Site
Majadahonda, 28222
Research Site
Murcia, 30008
Research Site
Santander, 39008
Israel8 sites
Research Site
Haifa, 31000
Research Site
Haifa, 31096
Research Site
Haifa, 34362
Research Site
Jerusalem, 9103102
Research Site
Nahariya, 22100
Research Site
Petah Tikvah, 49102
Research Site
Tel HaShomer, 52621
Research Site
Tiberias, 15208
Australia6 sites
Research Site
Darlinghurst, 2010
Research Site
Frankston, 3199
Research Site
Melbourne, 3000
Research Site
St Leonards, 2065
Research Site
Waratah NSW, 2298
Research Site
Wollongong, 2500
France6 sites
Research Site
Bobigny, 93000
Research Site
Créteil, 94010
Research Site
Pierre-Bénite, 69310
Research Site
Rennes, 35000
Research Site
Rouen, 76038
Research Site
Toulouse, 31059
Turkey (Türkiye)6 sites
Research Site
Ankara, 6230
Research Site
Ankara, 6560
Research Site
Instabul, 34365
Research Site
Izmir, 35040
Research Site
Izmir, 35340
Research Site
Kayseri, 38030
Belgium5 sites
Research Site
Bruges, 8000
Research Site
Brussels, 1200
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Research Site
Yvoir, 5530
Hungary4 sites
Research Site
Budapest, 1083
Research Site
Budapest, 1122
Research Site
Debrecen, 4032
Research Site
Kaposvár, 7400
New Zealand3 sites
Research Site
Addington, 8011
Research Site
Auckland, ?0620
Research Site
Tauranga, 3112
About this study
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
This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Acalabrutinib, Ibrutinib
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called ACP-196
Participants will receive oral acalabrutinib as stated in arm description.
IbrutinibDrug
Participants will receive oral ibrutinib as stated in arm description.
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib | Experimental | 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. Receives: Drug: Acalabrutinib |
| Ibrutinib | Active comparator | Participants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first. Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)
Secondary outcomes (10)
Number of Participants With Treatment-emergent Infections Grade >= 3
Number of participants with treatment-emergent infections Grade >=3 are reported.
Measured: Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Richter's Transformation
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.
Measured: Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Atrial Fibrillation
Number of participants with treatment-emergent atrial fibrillation (including atrial flutter) are reported.
Measured: Day 1 through 83.5 months (maximum observed duration)
Overall Survival (OS)
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.
Measured: 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)
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.
Measured: Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Treatment-emergent Laboratory Abnormalities
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.
Measured: Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
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).
Measured: Day 1 through 83.5 months (maximum observed duration)
Percentage of Participants With Lymphocytosis
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.
Measured: Day 1 through 83.5 months (maximum observed duration)
Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline
Number of participants with ECG abnormality at baseline are reported.
Measured: 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
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.
Measured: Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2015 (estimated)
- Study start28 Jul 2015
- Primary completion15 Sep 2020
- Study completion3 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Acerta Pharma BVThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 533 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acerta Pharma BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Acerta Clinical Trials, Study director, 1-888-292-9613
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02477696
- Sponsor's protocol ID
- ACE-CL-006
- Other IDs
- 2023-509347-27-00, 2014-005530-64, 2014, 2023
- Status last verified
- Aug 2026
- First submitted
- 12 Jun 2015
- Last updated
- 26 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40485230Alfaifi 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.
PubMed 39563886Woyach 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.
PubMed 38754046Seymour 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.
PubMed 37390310Kipps 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.
PubMed 34398557Byrd 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.
PubMed 34310172
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02477696
- Acronym / sponsor ID
- ACE-CL-006
- Conditions
- Chronic Lymphocytic Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 533 participants (actual)
- Lead sponsor
- Acerta Pharma BVIndustry (pharma, biotech, devices)
- Study start
- 28 Jul 2015 (actual)
- Primary completion
- 15 Sep 2020 (actual)
- Study completion
- 3 Jan 2028 (estimated)
- First posted
- 23 Jun 2015 (estimated)
- Results
- Posted 28 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib | Experimental | Drug: AcalabrutinibParticipants 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 comparator | Drug: IbrutinibParticipants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
- Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAlso: ACP-196Participants will receive oral acalabrutinib as stated in arm description. | Drug | Acalabrutinib |
| IbrutinibParticipants will receive oral ibrutinib as stated in arm description. | Drug | Ibrutinib |
Primary outcome
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.
10 secondary outcomes
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 Richter's Transformation
Time frame: 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)
Overall Survival (OS)
Time frame: 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)
Number of Participants With Treatment-emergent Laboratory Abnormalities
Time frame: 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)
Percentage of Participants With Lymphocytosis
Time frame: 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 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40485230Byrd 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.
- Derived from this study: PubMed 39563886Alfaifi 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.
- Derived from this study: PubMed 38754046Woyach 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.
- Derived from this study: PubMed 37390310Seymour 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.
- Derived from this study: PubMed 34398557Kipps 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.
- Derived from this study: PubMed 34310172Byrd 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.
- Redacted CSR SynopsisLink provided by the sponsor.
- Redacted CSPLink provided by the sponsor.
- Redacted SAPLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Chronic Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Acerta Clinical Trials study director
1-888-292-9613
130 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acalabrutinib and Ibrutinib in people with Chronic Lymphocytic Leukemia, run by Acerta Pharma BV at 130 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 130 sites in United States, United Kingdom, Netherlands, Italy, Poland and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02477696, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026; AzTrials last refreshed its copy on 8 Nov 2026.