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AzTrials

Chronic Lymphocytic LeukemiaPhase 1/2NCT02029443

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 study testing Acalabrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Acerta Pharma BV at 12 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Acalabrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
306 participants
Where
12 sitesin 3 countries
Study dates
30 Jan 2014to 9 Jun 2027
Phase
Phase 1/2
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 with a confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to, ≥ 2 previous treatments for CLL/SLL.
  • Must have measurable CLL/SLL defined as ≥ 1 lymph node ≥ 2 cm as measured in the longest diameter.
  • Active disease meeting ≥ 1 of the following International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment:
  • 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).
  • Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
  • Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
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  • 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.
  • Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
  • 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:
  • Unintentional weight loss ≥ 10% within the previous 6 months before screening.
  • Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before screening without evidence of infection.
  • Night sweats for > 1 month before screening without evidence of infection.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  • 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).
  • Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.

Who cannot join

  • 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.
  • 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.
  • 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%.
  • 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.
  • Any immunotherapy within 4 weeks of first dose of study drug.
  • 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).
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  • Relapsed after, or refractory to, prior BTK inhibitor therapy (Note: Does not apply to Ibrutinib R/R or Richter's Syndrome Group).
  • 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.

Trial locations and contacts

12 sites in 3 countries.

12 sites in 3 countries

United States8 sites

  • Research Site

    Boston, Massachusetts, 2215

  • Research Site

    Columbus, Ohio, 43210

  • Research Site

    Fort Worth, Texas, 76104

  • Research Site

    New Hyde Park, New York, 11042

  • Research Site

    New York, New York, 10021

  • Research Site

    Salt Lake City, Utah, 84112

  • Research Site

    Seattle, Washington, 98122

  • Research Site

    Tacoma, Washington, 98405

Other trials in United States

United Kingdom3 sites

  • Research Site

    Leeds, LS9 7TF

  • Research Site

    London, SE5 9RS

  • Research Site

    Oxford, OX3 7LE

Other trials in United Kingdom

Italy1 site

  • Research Site

    Milan, 20132

Other trials in Italy

About this study

Official title: A Phase 1/2, Multicenter, Open-label, and Dose-escalation Study of ACP-196 in Subjects With Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia

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).

Being tested
Acalabrutinib
Keywords
Bruton's tyrosine kinase inhibitor
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic

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 acalabrutinib as stated in the arms' description.

Study groups in NCT02029443
Study groupRoleWhat they receive
Relapsed/Refractory CohortExperimentalPhase 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.
Receives: Drug: Acalabrutinib
Treatment-naive CohortExperimentalTreatment-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.
Receives: Drug: Acalabrutinib
Ibrutinib-intolerant CohortExperimentalParticipants 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.
Receives: Drug: Acalabrutinib
Richters Syndrome/Prolymphocytic Leukemia Transformation CohortExperimentalParticipants 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.
Receives: Drug: Acalabrutinib
Ibrutinib Relapsed/Refractory CohortExperimentalParticipants 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.
Receives: Drug: Acalabrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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 (3)

  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.

    Measured: 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.

    Measured: 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2014 (estimated)
  2. Study start30 Jan 2014
  3. Primary completion15 Jul 2021
  4. Study completion9 Jun 2027 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
306 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02029443
Sponsor's protocol ID
ACE-CL-001
Other IDs
2023-509346-35-00, 2014-000440-15, 2014, 2023
Status last verified
May 2026
First submitted
6 Jan 2014
Last updated
5 May 2026
Data monitoring committee
No
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

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Acalabrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Acerta Pharma BV at 12 sites in 3 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 20 inclusion and 20 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 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, United Kingdom, Italy. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 10 Sep 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?

Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1 (time frame: From Day 1 to Day 28 after first dose of study drug). The study lists 14 primary outcomes in all. 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 NCT02029443, which also lists 9 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 5 May 2026.

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