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NCT Number: NCT02477696

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

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

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Chronic Lymphocytic Leukemia Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Darlinghurst, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men and women ≥ 18 years of age.
  • ECOG performance status of 0 to 2.
  • Diagnosis of CLL.
  • Must have ≥ 1 of the following high-risk prognostic factors:
  • Presence of 17p del by central laboratory.
  • Presence of 11q del by central laboratory.
  • Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment
  • Must have received ≥ 1 prior therapies for CLL.
  • Meet the following laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 750 cells/μL or ≥ 500 cells/μL in participants with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
  • Platelet count ≥ 30,000 cells/μL without transfusion support 7 days before assessment. Participants with transfusion-dependent thrombocytopenia are excluded.
  • Serum aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN).
  • Total bilirubin ≤ 1.5 x ULN.
  • Estimated creatinine clearance ≥ 30 mL/min.

Exclusion criteria

  • Known CNS lymphoma or leukemia.
  • Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  • Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor or a B-cell lymphoma-2 (BCL-2) inhibitor.
  • Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
  • Prior radio- or toxin-conjugated antibody therapy.
  • Prior allogeneic stem cell or autologous transplant.
  • Major surgery within 4 weeks before first dose of study drug.
  • Prior malignancy, except for adequately treated lentigo maligna melanoma, non-melanomatous skin cancer, in situ cervical carcinoma or other malignancy treated with no evidence of active disease > 3 years before Screening and at low risk for recurrence.
  • Significant cardiovascular disease within 6 months of screening.
  • Known history of infection with human immunodeficiency virus (HIV).
  • History of stroke or intracranial hemorrhage within 6 months before randomization.
  • History of bleeding diathesis.
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug.
  • Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor/inducer.

Treatment and study plan

Acalabrutinib

Drug

Participants will receive oral acalabrutinib as stated in arm description.

Other names: ACP-196

Ibrutinib

Drug

Participants will receive oral ibrutinib as stated in arm description.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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 infections Grade >=3 are reported.

  2. Number of Participants With Treatment-emergent Richter's Transformation

    Time frame: Day 1 through 83.5 months (maximum observed duration)

    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.

  3. Number of Participants With Treatment-emergent Atrial Fibrillation

    Time frame: Day 1 through 83.5 months (maximum observed duration)

    Number of participants with treatment-emergent atrial fibrillation (including atrial flutter) are reported.

  4. Overall Survival (OS)

    Time frame: Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)

    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.

  5. 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)

    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.

  6. Number of Participants With Treatment-emergent Laboratory Abnormalities

    Time frame: Day 1 through 83.5 months (maximum observed duration)

    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.

  7. Number of Participants With Abnormal Vital Signs Reported as TEAEs

    Time frame: Day 1 through 83.5 months (maximum observed duration)

    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).

  8. Percentage of Participants With Lymphocytosis

    Time frame: Day 1 through 83.5 months (maximum observed duration)

    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.

  9. Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline

    Time frame: Baseline (Days -28 to -1)

    Number of participants with ECG abnormality at baseline are reported.

  10. 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)

    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.

Sponsors and collaborators

Lead sponsor

Acerta Pharma BV

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2020
Study completion
2028
First posted
Jun 23, 2015
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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