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Active, not recruitingNCT02029443Updated May 5, 2026Results posted

ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia

A Phase 1/2 interventional study of Acalabrutinib in Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma and Richter's Syndrome, sponsored by Acerta Pharma BV. Active, not recruiting at 12 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-05.

Sponsored by Acerta Pharma BV · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
306
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This study is evaluating the safety and efficacy of a new BTK inhibitor, acalabrutinib, for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

02

Conditions studied

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Richter's Syndrome
  • Prolymphocytic Leukemia

Keywords

  • Bruton's tyrosine kinase inhibitor
03

In context

Leukemia, Lymphocytic, Chronic, B-Cell

1,603 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 243 are open to participants now.

This study's enrollment of 306 is above the median of 40 across 1,325 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.

Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →

Lead sponsor

Acerta Pharma BV is the lead sponsor of 40 studies on the registry; none are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 3 (25%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  1. Men and women ≥ 18 years of age with a confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to, ≥ 2 previous treatments for CLL/SLL.
  2. Must have measurable CLL/SLL defined as ≥ 1 lymph node ≥ 2 cm as measured in the longest diameter.

  3. Active disease meeting ≥ 1 of the following International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment:

    1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin \< 10 g/dL) and/or thrombocytopenia (platelets \< 100,000/μL).
    2. Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
    3. Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
    4. Progressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of \< 6 months. The LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In participants with initial blood lymphocyte counts of \< 30 X 10\^9/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
    5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
    6. Constitutional symptoms documented in the participant's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs:

    i. Unintentional weight loss ≥ 10% within the previous 6 months before screening.

    ii. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before screening without evidence of infection.

    iii. Night sweats for > 1 month before screening without evidence of infection.

  4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  5. Agreement to use highly effective methods of contraception during the study and for 2 days after the last dose of study drug if sexually active and able to bear or beget children (see Section 3.7.9 for list of highly effective methods of contraception).
  6. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
  7. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local participant privacy regulations).

Inclusion Criteria for Treatment Subgroups

  1. Treatment Naive only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL, who require treatment per National Cancer Institute (NCI) or International Working Group guidelines and a) do not want to receive chemoimmunotherapy or b) have comorbidities that would preclude chemoimmunotherapy.
  2. Ibrutinib Intolerant only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL who are not tolerating ibrutinib due to ibrutinib-related AEs.
  3. Richter's Syndrome/Prolymphocytic Leukemia Transformation only: Men and women ≥ 18 years of age and biopsy proven diffuse large B cell lymphoma (DLBCL) Richter's transformation or prolymphocytic leukemia transformation.
  4. Ibrutinib relapsed/refractory (R/R) only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL whose best response after 2 cycles of ibrutinib therapy was stable disease or nonresponse or who initially responded to ibrutinib therapy and now have signs of clinical progression.

Exclusion Criteria:

  1. Prior malignancy, except for adequately treated basal cell, squamous cell skin cancer or in situ cervical cancer. Participants with other prior malignancies from which the participant has been disease free for ≥ 2 years may be included if approved by the medical monitor.
  2. A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.
  3. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) ≤ 40%.
  4. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
  5. Any immunotherapy within 4 weeks of first dose of study drug.
  6. For participants with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s).
  7. Relapsed after, or refractory to, prior BTK inhibitor therapy (Note: Does not apply to Ibrutinib R/R or Richter's Syndrome Group).
  8. Any history of Richter's transformation (Note: Does not apply to Richter's Syndrome Group).

10. Central nervous system (CNS) involvement by lymphoma. 11. Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation.

12. Known history of human immunodeficiency virus (HIV) or serologic status indicating active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection or any uncontrolled active systemic infection. Participants with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded.

13. Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenic purpura (ITP) defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent).

14. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.

15. Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).

16. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.

17. Major surgery within 4 weeks before first dose of study drug. 18. ANC \< 0.75 x 10\^9/L or platelet count \< 50 x 10\^9/L unless there is bone marrow involvement.

19. Total bilirubin > 1.5 x upper limit of normal (ULN) (total bilirubin ≤ 2.5 x ULN allowed in participants with autoimmune hemolytic anemia that is otherwise controlled); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN unless disease related.

20. Serum amylase > 1.5 x ULN or serum lipase > 1.5 x ULN. 21. Significant screening electrocardiogram (ECG) abnormalities including, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, or QTc ≥ 480 ms.

22. Cardiac troponin I levels above the limit of normal as specified by the manufacturer.

23. Breast feeding or pregnant. 24. History of bleeding diathesis (eg, hemophilia, von Willebrand disease). 25. Concurrent participation in another therapeutic clinical trial. 26. Estimated creatinine clearance of \< 30 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female].

27. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
306 participants (actual)

Study arms

  • Experimental
    Relapsed/Refractory Cohort

    Phase 1 (dose-escalation) and Phase 2 (dose-expansion) will be conducted for participants with relapsed/refractory CLL or SLL. In Phase 1, participants will receive oral once daily (QD) acalabrutinib at Dose 1 (Cohort 1), Dose 2 (Cohort 2a), Dose 3 (Cohort 3), and Dose 4 (Cohort 4a), and twice daily (BID) acalabrutinib at Dose 1 (Cohort 2b) and Dose 5 (Cohort 4b) for 28 days (1 cycle). In Phase 2, participants will receive oral acalabrutinib at Dose 1 BID (Cohort 2b) or Dose 5 QD (Cohort 2c, later will be switched to Dose 1 BID per protocol amendment 6) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest. Participants from Phase 1 will be continued to receive Dose 1 BID until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

    Drug: Acalabrutinib

  • Experimental
    Treatment-naive Cohort

    Treatment-naïve participants with confirmed CLL or SLL, will receive oral acalabrutinib Dose 5 QD (Cohort 7, later will be switched to Dose 1 BID per protocol amendment 6) or Dose 1 BID (Cohort 11) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

    Drug: Acalabrutinib

  • Experimental
    Ibrutinib-intolerant Cohort

    Participants with confirmed CLL or SLL and were not tolerating ibrutinib treatment, will receive oral acalabrutinib Dose 5 QD (Cohort 8a, later switched to Dose 1 BID per protocol amendment 4) or Dose 1 BID (Cohort 8b) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

    Drug: Acalabrutinib

  • Experimental
    Richters Syndrome/Prolymphocytic Leukemia Transformation Cohort

    Participants with diffuse large B-cell lymphoma (DLBCL) Richter's transformation (RS) or prolymphocytic leukemia (PLL) transformation, will receive oral acalabrutinib Dose 5 BID (Cohort 9) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

    Drug: Acalabrutinib

  • Experimental
    Ibrutinib Relapsed/Refractory Cohort

    Participants with confirmed CLL/SLL and had relapsed/refractory to ibrutinib treatment, will receive oral acalabrutinib Dose 5 QD (Cohort 10) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

    Drug: Acalabrutinib

Interventions

  • DrugAcalabrutinib

    Participants will receive acalabrutinib as stated in the arms' description.

    Also known as: ACP-196

06

What researchers measure

Primary outcomes

  1. Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1

    Participants with DLTs in Phase 1 are reported. The DLT was defined as any of the following events unless the adverse event is clearly related to disease progression or the participant's current medical history and associated comorbidities: (1) Any Grade 3 or greater nonhematologic toxicity with the exceptions of alopecia and Grade 3 nausea, vomiting, and diarrhea that respond to supportive therapy; (2) Hematologic toxicities including Grade 4 neutropenia lasting more than 5 days, Grade 4 or Grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion, Grade 3 or greater febrile neutropenia (body temperature of 38.5 degrees Celsius or more), or Grade 4 anemia, unexplained by underlying disease; or (3) Dosing delay due to toxicity for \> 7 consecutive days.

    Time frame: From Day 1 to Day 28 after first dose of study drug

  2. 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.

    Time frame: Day 1 through the final data cutoff date (approximately 7 years 6 months)

  3. Number of Participants With Treatment Emergent Events of Clinical Interest (ECI)

    The treatment emergent ECI included the events identified based on preclinical findings, emerging data from clinical studies relating to acalabrutinib, and pharmacological effects of approved Bruton's tyrosine kinase (BTK) inhibitors and reported after the first dose of the study drug.

    Time frame: Day 1 through the final data cutoff date (approximately 7 years 6 months)

  4. Number of Participants With Clinically Important Laboratory Abnormalities With Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or More

    Participants with clinically important laboratory abnormalities with CTCAE Grade 3 or more are reported. Laboratory analysis included hematology, clinical chemistry, amylase, lipase, cardiac troponin I, hepatitis B and C testing, and urinalysis. The CTCAE version 4.03 is a descriptive terminology is used for AE reporting. The CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death related to AE.

    Time frame: Day 1 through the final data cutoff date (approximately 7 years 6 months)

  5. Number of Participants With Clinically Abnormal Vital Signs Reported as TEAEs

    Participants with clinically abnormal vital signs (blood pressure, respiratory rate, pulse rate, or body temperature) reported as TEAEs are reported.

    Time frame: Day 1 through the final data cutoff date (approximately 7 years 6 months)

  6. Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of Acalabrutinib

    The AUC0-6 of acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours postdose on Day 1 and Day 8

  7. Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Acalabrutinib

    The AUC0-last of acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

  8. Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib

    The AUC0-inf of Acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

  9. Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib

    The Cmax of Acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

  10. Time of Maximum Plasma Concentration (Tmax) of Acalabrutinib

    The Tmax of Acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

  11. Terminal Elimination Half-life (t1/2) of Acalabrutinib

    The t1/2 of acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

  12. Terminal Elimination Rate Constant (λz) of Acalabrutinib

    The λz of acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

  13. Apparent Oral Clearance (CL/F) of Acalabrutinib

    The CL/F of acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

  14. Apparent Volume of Distribution (Vz/F) of Acalabrutinib

    The Vz/F of acalabrutinib is reported.

    Time frame: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Secondary outcomes

  1. Percentage of Participants With Objective Response (OR) as Assessed by the Investigator

    For CLL/SLL, OR is defined as complete remission (CR), CR with incomplete marrow recovery (CRi), or partial remission (PR). CR: lymphocytes (lympho) \<4×10\^9/L, normocellular bone marrow (BM), normal lymph nodes (NLN), liver and spleen (L/S), absolute neutrophil count (ANC) \>1.5×10\^9/L, platelets \>100×10\^9/L, hemoglobin (Hb) \>11g/dL. Cri: lympho \<4×10\^9/L, hypocellular BM, NLN, L/S, persistent anemia, hrombocytopenia, or neutropenia. PR: \>=50% reduction in lymphadenopathy and/or enlargement of L/S or lympho (\<5×10\^9/L or \>=50% decrease from baseline) and criteria of ANC/platelets/Hb per CR or \>=50% improvement over baseline. Hematology result were without exogenous growth factors/transfusion. For RS, OR as CR or PR by Cheson et al. 2014 based on PET/CT scans and bone marrow. CR: disappearance of all detectable clinical evidence of disease and disease-related symptoms and PR: \>=50% decrease in sum of the product diameter of 6 largest nodal masses and no new sites of disease.

    Time frame: Day 1 through the final data cutoff date (approximately 7 years 6 months)

  2. Duration of Response (DOR) as Assessed by the Investigator

    The DoR is defined as the time from the date of achieving the first CR, CRi, or PR to the date of progressive disease (PD) or death due to any cause, whichever occurred first. The CR, CRi, or PR are defined in the above outcome measure. For CLL/SLL, PD is defined as lympho \>=50% increase from baseline with \>= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or \>= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of \>=50% from baseline secondary to CLL or \< 100,000/µL and worsening bone marrow or Hb decrease of \> 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The DoR was estimated using Kaplan-Meier method.

    Time frame: Day 1 through the final data cutoff date (approximately 7 years 6 months)

  3. Progression Free Survival (PFS) as Assessed by the Investigator

    The PFS is defined as the time from the date of first dose of study drug to the date of first PD or death due to any cause, whichever occurred first. For CLL/SLL, PD is defined as lympho \>= 50 % increase from baseline with \>= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or \>= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of \>= 50 % from baseline secondary to CLL or \< 100,000/µL and worsening bone marrow or Hb decrease of \> 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The PFS was estimated using Kaplan-Meier method.

    Time frame: Day 1 through the final data cutoff date (approximately 7 years 6 months)

07

Results

Posted Sep 10, 2022
Limitations and caveats
The Phase 2 dose was chosen on the basis of the pharmacodynamics data.

Participant flow

Participant flow — Overall Study
MilestoneRelapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory Cohort
Started1349933296
Completed4170630
Not completed932927266
Withdrew: Completed 30-day safety follow-up visit53161221
Withdrew: Death1322112
Withdrew: Lost to follow-up10110
Withdrew: Started other anti-cancer therapy174793
Withdrew: Withdrawal by subject31110
Withdrew: Other66420

Outcome measures

PrimaryNumber of Participants With Dose Limiting Toxicities (DLTs) in Phase 1

Participants with DLTs in Phase 1 are reported. The DLT was defined as any of the following events unless the adverse event is clearly related to disease progression or the participant's current medical history and associated comorbidities: (1) Any Grade 3 or greater nonhematologic toxicity with the exceptions of alopecia and Grade 3 nausea, vomiting, and diarrhea that respond to supportive therapy; (2) Hematologic toxicities including Grade 4 neutropenia lasting more than 5 days, Grade 4 or Grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion, Grade 3 or greater febrile neutropenia (body temperature of 38.5 degrees Celsius or more), or Grade 4 anemia, unexplained by underlying disease; or (3) Dosing delay due to toxicity for \> 7 consecutive days.

Time frame:
From Day 1 to Day 28 after first dose of study drug
Reported as:
Count of participants · Participants
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1
ParticipantsCohort 1Cohort 2aCohort 2bCohort 3Cohort 4aCohort 4b
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1000000
PrimaryNumber 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.

Time frame:
Day 1 through the final data cutoff date (approximately 7 years 6 months)
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
ParticipantsRelapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory Cohort
Any TEAEs1349933286
Any TESAEs865020183
PrimaryNumber of Participants With Treatment Emergent Events of Clinical Interest (ECI)

The treatment emergent ECI included the events identified based on preclinical findings, emerging data from clinical studies relating to acalabrutinib, and pharmacological effects of approved Bruton's tyrosine kinase (BTK) inhibitors and reported after the first dose of the study drug.

Time frame:
Day 1 through the final data cutoff date (approximately 7 years 6 months)
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Events of Clinical Interest (ECI)
ParticipantsRelapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory Cohort
Atrial fibrillation126430
Ventricular tachyarrhythmias20000
Anemia22104101
Neutropenia2695131
Other Leukopenia21100
Thrombocytopenia101440
Major hemorrhage118401
Hepatotoxicity44130
Hypertension3129720
Infections1188625184
Interstitial lung disease/Pneumonitis13000
Second primary malignancies, excluding non-melanoma skin2314310
Tumor lysis syndrome10000
PrimaryNumber of Participants With Clinically Important Laboratory Abnormalities With Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or More

Participants with clinically important laboratory abnormalities with CTCAE Grade 3 or more are reported. Laboratory analysis included hematology, clinical chemistry, amylase, lipase, cardiac troponin I, hepatitis B and C testing, and urinalysis. The CTCAE version 4.03 is a descriptive terminology is used for AE reporting. The CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death related to AE.

Time frame:
Day 1 through the final data cutoff date (approximately 7 years 6 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Important Laboratory Abnormalities With Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or More
ParticipantsRelapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory Cohort
Hemoglobin, platelets or neutrophils decreased723014194
Absolute neutrophil count (decreased)572311133
Hemoglobin (decreased)175383
Platelets (decreased)203451
Leukocytes (decreased)122360
Leukocytes (increased)2921702
Absolute lymphocyte count (decreased)207260
Absolute lymphocyte count (increased)298731
Urate (increased)2415852
Sodium (decreased)125230
Phosphate (decreased)91110
Potassium (increased)35100
Glucose (increased)31300
Alanine aminotransferase (increased)31110
Calcium (increased)50010
Aspartate aminotransferase (increased)22000
Magnesium (increased)22000
Potassium (decreased)21010
Albumin (decreased)21000
Calcium (decreased)20010
Alkaline phosphatase (increased)10010
Amylase (increased)20000
Bilirubin (increased)20000
Creatinine (increased)20000
Lipase (increased)11000
PrimaryNumber of Participants With Clinically Abnormal Vital Signs Reported as TEAEs

Participants with clinically abnormal vital signs (blood pressure, respiratory rate, pulse rate, or body temperature) reported as TEAEs are reported.

Time frame:
Day 1 through the final data cutoff date (approximately 7 years 6 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Abnormal Vital Signs Reported as TEAEs
ParticipantsRelapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory Cohort
Tachycardia38230
Bradycardia61000
Pyrexia39141060
Hyperpyrexia00010
Hypothermia01000
Procedural hypotension01000
Blood pressure increased01000
Dyspnoea2718632
Dyspnoea exertional55101
Hypertension3028610
Hypotension712512
Orthostatic hypotension05100
Essential hypertension00100
Hypertensive crisis10000
Malignant hypertension00010
Palpitations134000
PrimaryArea Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of Acalabrutinib

The AUC0-6 of acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours postdose on Day 1 and Day 8
Reported as:
Mean · hr*ng/mL
Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of Acalabrutinib
hr*ng/mLCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 1971 ± 5641250 ± 836819 ± 4932170 ± 11801880 ± 18102960 ± 15701950 ± 4871740 ± 1540362 ± 221670 ± 4711690 ± 8491100 ± 590789 ± 398
Day 8631 ± 1931180 ± 859858 ± 4191660 ± 5541750 ± 5181630 ± 10501690 ± 10901480 ± 9862080 ± NA834 ± 7131860 ± 7861250 ± 1050642 ± 310
PrimaryArea Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Acalabrutinib

The AUC0-last of acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Mean · hr*ng/mL
Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Acalabrutinib
hr*ng/mLCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 11030 ± 5291270 ± 775795 ± 5022280 ± 10602030 ± 16703430 ± 16401950 ± 4871790 ± 1470539 ± 106570 ± 4511860 ± 15701100 ± 590850 ± 462
Day 8729 ± 3801180 ± 861850 ± 6601850 ± 8822020 ± 11701750 ± 9791560 ± 10201400 ± 9291180 ± NA748 ± 7011710 ± 6691260 ± 1060660 ± 294
PrimaryArea Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib

The AUC0-inf of Acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Mean · hr*ng/mL
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib
hr*ng/mLCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 11040 ± 5341320 ± 827855 ± 5172440 ± 10102050 ± 16803250 ± 16301970 ± 4951910 ± 1530574 ± 76.3801 ± 4101770 ± 7761350 ± 373940 ± 430
Day 8621 ± 1871200 ± 865956 ± 6651990 ± 10202360 ± 12101750 ± 11401780 ± 12301540 ± 9732120 ± NA963 ± 7281750 ± 7011580 ± 1030652 ± 298
PrimaryMaximum Observed Plasma Concentration (Cmax) of Acalabrutinib

The Cmax of Acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib
ng/mLCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 1685 ± 475754 ± 540706 ± 4991950 ± 14601350 ± 11701550 ± 12301600 ± 2911390 ± 1260206 ± 240554 ± 5001190 ± 925727 ± 436930 ± 595
Day 8521 ± 308805 ± 757812 ± 8291350 ± 8091350 ± 933902 ± 6381320 ± 15401020 ± 747939 ± NA616 ± 6601460 ± 913610 ± 751633 ± 449
PrimaryTime of Maximum Plasma Concentration (Tmax) of Acalabrutinib

The Tmax of Acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Median · Hours
Time of Maximum Plasma Concentration (Tmax) of Acalabrutinib
HoursCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 11.01 (0.417 to 2.00)0.917 (0.500 to 3.83)0.750 (0.500 to 2.30)1.00 (0.250 to 5.92)1.00 (0.500 to 1.83)1.00 (0.750 to 4.00)0.758 (0.250 to 1.08)0.783 (0.250 to 2.10)1.30 (0.750 to 2.20)0.783 (0.500 to 5.83)0.992 (0.500 to 4.05)1.00 (0.500 to 1.08)0.642 (0.483 to 2.00)
Day 81.05 (0.500 to 1.17)0.517 (0.467 to 1.00)0.750 (0.450 to 5.75)1.03 (0.500 to 2.10)1.00 (0.500 to 1.97)0.700 (0.500 to 1.95)0.758 (0.500 to 2.07)0.750 (0.250 to 2.22)1.49 (1.08 to 1.90)0.908 (0.467 to 2.03)1.00 (0.500 to 2.08)1.58 (0.467 to 4.08)0.533 (0.250 to 1.85)
PrimaryTerminal Elimination Half-life (t1/2) of Acalabrutinib

The t1/2 of acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Mean · Hours
Terminal Elimination Half-life (t1/2) of Acalabrutinib
HoursCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 11.48 ± 1.501.44 ± 1.600.914 ± 0.4520.993 ± 0.3032.89 ± 3.123.52 ± 4.930.869 ± 0.08111.41 ± 1.734.83 ± 3.690.900 ± 0.1400.798 ± 0.09731.01 ± 0.2090.781 ± 0.137
Day 81.09 ± 0.2160.942 ± 0.1070.995 ± 0.6210.902 ± 0.1870.886 ± 0.1311.38 ± 0.5461.13 ± 0.4081.02 ± 0.4540.914 ± NA1.25 ± 0.4940.867 ± 0.2891.67 ± 1.410.811 ± 0.174
PrimaryTerminal Elimination Rate Constant (λz) of Acalabrutinib

The λz of acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Mean · 1/hr
Terminal Elimination Rate Constant (λz) of Acalabrutinib
1/hrCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 10.679 ± 0.2760.750 ± 0.3070.848 ± 0.2140.755 ± 0.2090.502 ± 0.3000.557 ± 0.3860.804 ± 0.07930.756 ± 0.2920.373 ± 0.4680.784 ± 0.1120.880 ± 0.1140.706 ± 0.1440.916 ± 0.177
Day 80.655 ± 0.1320.744 ± 0.08660.793 ± 0.1910.798 ± 0.1610.797 ± 0.1280.578 ± 0.2430.679 ± 0.2510.745 ± 0.1740.758 ± NA0.623 ± 0.2180.857 ± 0.2090.603 ± 0.3240.894 ± 0.204
PrimaryApparent Oral Clearance (CL/F) of Acalabrutinib

The CL/F of acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Mean · L/hr
Apparent Oral Clearance (CL/F) of Acalabrutinib
L/hrCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 1114 ± 44.4193 ± 121212 ± 302112 ± 98.4265 ± 263169 ± 123108 ± 32.0315 ± 488352 ± 43.7311 ± 166142 ± 88.9156 ± 40.3137 ± 77.4
Day 8176 ± 62.1216 ± 154162 ± 141122 ± 55.5131 ± 70.3344 ± 242191 ± 180389 ± 107094.5 ± NA336 ± 258132 ± 51.8167 ± 95.1188 ± 92.5
PrimaryApparent Volume of Distribution (Vz/F) of Acalabrutinib

The Vz/F of acalabrutinib is reported.

Time frame:
Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8
Reported as:
Mean · L
Apparent Volume of Distribution (Vz/F) of Acalabrutinib
LCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 8aCohort 8bCohort 9Cohort 10Cohort 11
Day 1268 ± 332574 ± 992450 ± 1250182 ± 2302100 ± 32901480 ± 2850133 ± 30.0930 ± 17502600 ± 2030422 ± 290171 ± 125235 ± 105158 ± 102
Day 8286 ± 150302 ± 238333 ± 729165 ± 104172 ± 114739 ± 745384 ± 4661180 ± 4940125 ± NA726 ± 814179 ± 134533 ± 716234 ± 162
SecondaryPercentage of Participants With Objective Response (OR) as Assessed by the Investigator

For CLL/SLL, OR is defined as complete remission (CR), CR with incomplete marrow recovery (CRi), or partial remission (PR). CR: lymphocytes (lympho) \<4×10\^9/L, normocellular bone marrow (BM), normal lymph nodes (NLN), liver and spleen (L/S), absolute neutrophil count (ANC) \>1.5×10\^9/L, platelets \>100×10\^9/L, hemoglobin (Hb) \>11g/dL. Cri: lympho \<4×10\^9/L, hypocellular BM, NLN, L/S, persistent anemia, hrombocytopenia, or neutropenia. PR: \>=50% reduction in lymphadenopathy and/or enlargement of L/S or lympho (\<5×10\^9/L or \>=50% decrease from baseline) and criteria of ANC/platelets/Hb per CR or \>=50% improvement over baseline. Hematology result were without exogenous growth factors/transfusion. For RS, OR as CR or PR by Cheson et al. 2014 based on PET/CT scans and bone marrow. CR: disappearance of all detectable clinical evidence of disease and disease-related symptoms and PR: \>=50% decrease in sum of the product diameter of 6 largest nodal masses and no new sites of disease.

Time frame:
Day 1 through the final data cutoff date (approximately 7 years 6 months)
Reported as:
Number · Percentage of participants
Percentage of Participants With Objective Response (OR) as Assessed by the Investigator
Percentage of participantsCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 11
Percentage of Participants With Objective Response (OR) as Assessed by the Investigator100.0 (63.1 to 100.0)75 (34.9 to 96.8)92.1 (82.4 to 97.4)93.8 (79.2 to 99.2)100.0 (59.0 to 100.0)100.0 (54.1 to 100.0)100.0 (54.1 to 100.0)97.3 (85.8 to 99.9)100.0 (94.0 to 100.0)
SecondaryDuration of Response (DOR) as Assessed by the Investigator

The DoR is defined as the time from the date of achieving the first CR, CRi, or PR to the date of progressive disease (PD) or death due to any cause, whichever occurred first. The CR, CRi, or PR are defined in the above outcome measure. For CLL/SLL, PD is defined as lympho \>=50% increase from baseline with \>= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or \>= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of \>=50% from baseline secondary to CLL or \< 100,000/µL and worsening bone marrow or Hb decrease of \> 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The DoR was estimated using Kaplan-Meier method.

Time frame:
Day 1 through the final data cutoff date (approximately 7 years 6 months)
Reported as:
Median · Months
Duration of Response (DOR) as Assessed by the Investigator
MonthsCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 11
Duration of Response (DOR) as Assessed by the Investigator33.3 (13.8 to NA)26.7 (13.9 to NA)77.3 (46.3 to NA)43.0 (29.4 to NA)NA (9.0 to NA)64.1 (19.4 to NA)NA (38.9 to NA)NA (NA to NA)NA (NA to NA)
SecondaryProgression Free Survival (PFS) as Assessed by the Investigator

The PFS is defined as the time from the date of first dose of study drug to the date of first PD or death due to any cause, whichever occurred first. For CLL/SLL, PD is defined as lympho \>= 50 % increase from baseline with \>= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or \>= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of \>= 50 % from baseline secondary to CLL or \< 100,000/µL and worsening bone marrow or Hb decrease of \> 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The PFS was estimated using Kaplan-Meier method.

Time frame:
Day 1 through the final data cutoff date (approximately 7 years 6 months)
Reported as:
Median · Months
Progression Free Survival (PFS) as Assessed by the Investigator
MonthsCohort 1Cohort 2aCohort 2bCohort 2cCohort 3Cohort 4aCohort 4bCohort 7Cohort 11
Progression Free Survival (PFS) as Assessed by the Investigator38.3 (15.5 to NA)33.1 (15.8 to NA)79.1 (49.8 to NA)46.6 (33.9 to NA)NA (12.7 to NA)67.8 (33.2 to NA)NA (40.7 to NA)NA (NA to NA)NA (NA to NA)

Adverse events

Collected over Day 1 through the final data cutoff date (approximately 7 years 6 months). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Relapsed/Refractory Cohort13/134 (9.7%)86/134 (64.2%)134/134 (100%)
Treatment-naive Cohort2/99 (2%)50/99 (50.5%)99/99 (100%)
Ibrutinib-intolerant Cohort2/33 (6.1%)20/33 (60.6%)33/33 (100%)
Richters Syndrome/Prolymphocytic Leukemia Transformation Cohort11/29 (37.9%)18/29 (62.1%)28/29 (96.6%)
Ibrutinib Relapsed/Refractory Cohort2/6 (33.3%)3/6 (50%)6/6 (100%)
Most frequent serious events
Showing 10 of 203
Most frequent serious events
EventRelapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory Cohort
Abdominal painGastrointestinal disorders3/1340/991/330/291/6
DiarrhoeaGastrointestinal disorders4/1341/990/330/291/6
SepsisInfections and infestations3/1342/990/332/291/6
Septic shockInfections and infestations0/1340/990/330/291/6
Upper respiratory tract infectionInfections and infestations2/1340/991/330/291/6
Haemorrhage intracranialNervous system disorders0/1340/990/330/291/6
PneumoniaInfections and infestations19/1346/993/331/290/6
Febrile neutropeniaBlood and lymphatic system disorders3/1341/991/333/290/6
HypercalcaemiaMetabolism and nutrition disorders4/1340/990/333/290/6
FatigueGeneral disorders0/1341/990/332/290/6
Most frequent other events
Showing 10 of 924
Most frequent other events
EventRelapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory Cohort
DiarrhoeaGastrointestinal disorders71/13453/9920/3314/290/6
ArthralgiaMusculoskeletal and connective tissue disorders47/13455/999/336/290/6
HeadacheNervous system disorders68/13448/9914/3312/291/6
ContusionInjury, poisoning and procedural complications42/13450/9911/335/290/6
Upper respiratory tract infectionInfections and infestations54/13449/9915/333/291/6
CoughRespiratory, thoracic and mediastinal disorders47/13432/9913/334/291/6
FatigueGeneral disorders49/13422/997/336/291/6
NauseaGastrointestinal disorders47/13434/9911/334/292/6
HypotensionVascular disorders7/13411/995/331/292/6
Weight increasedInvestigations34/13433/9910/330/290/6

Baseline characteristics

All-treated population included all enrolled participants who received 1 or more doses of study drug.

Age, Continuous
Age, Continuous(Years)Relapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory CohortTotal
Mean65.6 ± 9.263.5 ± 9.763.9 ± 8.965.0 ± 9.662.5 ± 7.964.6 ± 9.33
Sex: Female, Male
Sex: Female, Male(Participants)Relapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory CohortTotal
Female35331314398
Male996620153203
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Relapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory CohortTotal
Hispanic or Latino230005
Not Hispanic or Latino1299433286290
Unknown or Not Reported320106
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Relapsed/Refractory CohortTreatment-naive CohortIbrutinib-intolerant CohortRichters Syndrome/Prolymphocytic Leukemia Transformation CohortIbrutinib Relapsed/Refractory CohortTotal
American Indian or Alaska Native100001
Asian120003
Native Hawaiian or Other Pacific Islander000000
Black or African American6521115
White1208831275271
More than one race6401011
Unknown or Not Reported000000
08

Study locations

12 sites
  • Research Site
    Boston, Massachusetts 2215, United States
  • Research Site
    New Hyde Park, New York 11042, United States
  • Research Site
    New York, New York 10021, United States
  • Research Site
    Columbus, Ohio 43210, United States
  • Research Site
    Fort Worth, Texas 76104, United States
  • Research Site
    Salt Lake City, Utah 84112, United States
  • Research Site
    Seattle, Washington 98122, United States
  • Research Site
    Tacoma, Washington 98405, United States
  • Research Site
    Milan, 20132, Italy
  • Research Site
    Leeds, LS9 7TF, United Kingdom
  • Research Site
    London, SE5 9RS, United Kingdom
  • Research Site
    Oxford, OX3 7LE, United Kingdom
09

References and documents

Publications

  • Furman RR, Wierda WG, Patten PEM, Chaves JM, Brown JR, Munir T, Martin P, Awan FT, Stephens DM, Ghia P, Barrientos JC, Patel K, Woyach JA, de Borja M, Wang MH, Jain N, O'Brien SM, Byrd JC. Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia. Blood Adv. 2026 Jun 9;10(11):3931-3941. doi: 10.1182/bloodadvances.2025018310. PubMed 41915892 ↗
  • Nuttall B, Karl DL, Burke K, Callahan M, Mendler K, Cingolani P, Criscione S, Naumenko S, Bibikova E, Munugalavadla V, Byrd JC, Furman RR, Brown JR, Mortlock A, Dougherty BA, Carl Barrett J, Scaltriti M, Hadfield J. Comprehensive comparison of enzymatic and bisulfite DNA methylation analysis in clinically relevant samples. Clin Epigenetics. 2025 Oct 3;17(1):156. doi: 10.1186/s13148-025-01959-0. PubMed 41044668 ↗
  • Bibikova E, Parsa S, Floren M, Law B, Clevenger T, Cheung J, De Jesus G, Burke K, Gulrajani M, Yamaguchi K, Do P, Dougherty B, Whitston D, Brock G, Munugalavadla V, Frigault MM, Hartmann TN, Byrd JC, Furman RR, Brown JR, Covey T, Mortlock A. Molecular Profiling Identifies CD49d and CD79b as Predictive Markers for Acquired Acalabrutinib Resistance in Patients With Chronic Lymphocytic Leukemia. Hematol Oncol. 2025 Jan;43(1):e70008. doi: 10.1002/hon.70008. PubMed 39716442 ↗
  • 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. PubMed 39563886 ↗
  • Eyre TA, Schuh A, Wierda WG, Brown JR, Ghia P, Pagel JM, Furman RR, Cheung J, Hamdy A, Izumi R, Patel P, Wang MH, Xu Y, Byrd JC, Hillmen P. Acalabrutinib monotherapy for treatment of chronic lymphocytic leukaemia (ACE-CL-001): analysis of the Richter transformation cohort of an open-label, single-arm, phase 1-2 study. Lancet Haematol. 2021 Dec;8(12):e912-e921. doi: 10.1016/S2352-3026(21)00305-7. Epub 2021 Nov 1. PubMed 34735860 ↗
  • Byrd JC, Wierda WG, Schuh A, Devereux S, Chaves JM, Brown JR, Hillmen P, Martin P, Awan FT, Stephens DM, Ghia P, Barrientos J, Pagel JM, Woyach JA, Burke K, Covey T, Gulrajani M, Hamdy A, Izumi R, Frigault MM, Patel P, Rothbaum W, Wang MH, O'Brien S, Furman RR. Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results. Blood. 2020 Apr 9;135(15):1204-1213. doi: 10.1182/blood.2018884940. PubMed 31876911 ↗
  • Awan FT, Schuh A, Brown JR, Furman RR, Pagel JM, Hillmen P, Stephens DM, Woyach J, Bibikova E, Charuworn P, Frigault MM, Hamdy A, Izumi R, Linghu B, Patel P, Wang MH, Byrd JC. Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib. Blood Adv. 2019 May 14;3(9):1553-1562. doi: 10.1182/bloodadvances.2018030007. PubMed 31088809 ↗
  • Long M, Beckwith K, Do P, Mundy BL, Gordon A, Lehman AM, Maddocks KJ, Cheney C, Jones JA, Flynn JM, Andritsos LA, Awan F, Fraietta JA, June CH, Maus MV, Woyach JA, Caligiuri MA, Johnson AJ, Muthusamy N, Byrd JC. Ibrutinib treatment improves T cell number and function in CLL patients. J Clin Invest. 2017 Aug 1;127(8):3052-3064. doi: 10.1172/JCI89756. Epub 2017 Jul 17. PubMed 28714866 ↗
  • Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):323-32. doi: 10.1056/NEJMoa1509981. Epub 2015 Dec 7. PubMed 26641137 ↗

Study documents

  • Study protocol · Aug 25, 2021
  • Statistical analysis plan · Aug 25, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Sap

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 5, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02029443
Lead sponsor
Acerta Pharma BV
Responsible party
Sponsor
First posted
Jan 8, 2014
Start date
Jan 30, 2014
Primary completion
Jul 15, 2021
Completion
Jun 9, 2027 (estimated)
Results posted
Sep 10, 2022
Last update
May 5, 2026

Study contacts

Acerta Clinical Trials
study director · 1-888-292-9613 acertamc@dlss.com

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.

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