Chronic Lymphocytic Leukemia
Conditions
Brief summary
This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.
Interventions
DRUGAcalabrutinib
Participants will receive oral acalabrutinib as stated in arm description.
DRUGIbrutinib
Participants will receive oral ibrutinib as stated in arm description.
Sponsors
Acerta Pharma BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Infections Grade >= 3 | Day 1 through 83.5 months (maximum observed duration) | Number of participants with treatment-emergent infections Grade \>=3 are reported. |
| Number of Participants With Treatment-emergent Richter's Transformation | 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. |
| Number of Participants With Treatment-emergent Atrial Fibrillation | Day 1 through 83.5 months (maximum observed duration) | Number of participants with treatment-emergent atrial fibrillation (including atrial flutter) are reported. |
| Overall Survival (OS) | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Day 1 through 83.5 months (maximum observed duration) | 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. |
| Number of Participants With Treatment-emergent Laboratory Abnormalities | 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. |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs | 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). |
| Percentage of Participants With Lymphocytosis | 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. |
| Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline | Baseline (Days -28 to -1) | Number of participants with ECG abnormality at baseline are reported. |
| Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | 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. |
Countries
Australia, Belgium, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORAcerta Clinical Trials
1-888-292-9613
Participant flow
Pre-assignment details
A total of 533 participants were randomized in this study of which 529 participants were treated (4 participants were randomized but not treated).
Participants by arm
| Arm | Count |
|---|---|
| Acalabrutinib Participants received oral acalabrutinib (ACP196) 100 mg BID until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurred first. | 268 |
| Ibrutinib Participants received oral ibrutinib 420 mg QD until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurred first. | 265 |
| Total | 533 |
Baseline characteristics
| Characteristic | Ibrutinib | Total | Acalabrutinib |
|---|---|---|---|
| Age, Continuous Age (years) | 65.3 Years STANDARD_DEVIATION 9.6 | 65.4 Years STANDARD_DEVIATION 9.4 | 65.5 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 13 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 472 Participants | 235 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 23 Participants | 48 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 15 Participants | 5 Participants |
| Race (NIH/OMB) White | 245 Participants | 502 Participants | 257 Participants |
| Sex: Female, Male Sex Female | 71 Participants | 154 Participants | 83 Participants |
| Sex: Female, Male Sex Male | 194 Participants | 379 Participants | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 89 / 266 | 106 / 263 |
| other Total, other adverse events | 251 / 266 | 251 / 263 |
| serious Total, serious adverse events | 161 / 266 | 177 / 263 |
Outcome results
Primary
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.
Time frame: Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)
Population: ITT population included all participants randomized and were analyzed according to the arm to which they were randomly assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acalabrutinib | Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment | 38.4 Months |
| Ibrutinib | Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment | 38.4 Months |
95% CI: [0.79, 1.27]
Secondary
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).
Time frame: Day 1 through 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure fluctuation | 0 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Heart rate increased | 0 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Body temperature increased | 0 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Heart rate irregular | 1 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure decreased | 1 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 26 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Bradycardia | 3 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 15 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Abnormal loss of weight | 0 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hyperpyrexia | 1 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 2 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure systolic increased | 0 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 12 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Cardiac murmur | 1 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 66 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure increased | 2 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Dyspnoea | 40 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 29 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Body temperature decreased | 1 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 13 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Dyspnoea exertional | 2 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | White coat hypertension | 0 Participants |
| Acalabrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia | 7 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | White coat hypertension | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Abnormal loss of weight | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure fluctuation | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure increased | 3 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure decreased | 0 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure systolic increased | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Body temperature decreased | 0 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Body temperature increased | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Bradycardia | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Breath sounds abnormal | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Cardiac murmur | 2 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Dyspnoea | 27 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Dyspnoea exertional | 5 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Heart rate increased | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Heart rate irregular | 0 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 70 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 7 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hyperpyrexia | 0 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 1 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 15 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 55 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia | 7 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 23 Participants |
| Ibrutinib | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 10 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline
Number of participants with ECG abnormality at baseline are reported.
Time frame: Baseline (Days -28 to -1)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acalabrutinib | Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline | Abnormal, not clinically significant | 86 Participants |
| Acalabrutinib | Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline | Abnormal, clinically significant | 4 Participants |
| Ibrutinib | Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline | Abnormal, not clinically significant | 98 Participants |
| Ibrutinib | Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline | Abnormal, clinically significant | 1 Participants |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated. Here, number of participants analyzed (N) signified those participants who had a baseline value and at least 1 postbaseline value of ECOG performance status score during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acalabrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=0; Postbaseline=3 | 0 Participants |
| Acalabrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=1; Postbaseline=3 | 3 Participants |
| Acalabrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=2; Postbaseline=3 | 4 Participants |
| Acalabrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=0; Postbaseline=4 | 0 Participants |
| Acalabrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=1; Postbaseline=4 | 0 Participants |
| Acalabrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=2; Postbaseline=4 | 0 Participants |
| Ibrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=1; Postbaseline=4 | 0 Participants |
| Ibrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=0; Postbaseline=3 | 1 Participants |
| Ibrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=0; Postbaseline=4 | 0 Participants |
| Ibrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=1; Postbaseline=3 | 5 Participants |
| Ibrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=2; Postbaseline=4 | 0 Participants |
| Ibrutinib | Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status | Baseline=2; Postbaseline=3 | 1 Participants |
Secondary
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 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acalabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAEs | 262 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAEs | 161 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAEs | 259 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAEs | 177 Participants |
Secondary
Number of Participants With Treatment-emergent Atrial Fibrillation
Number of participants with treatment-emergent atrial fibrillation (including atrial flutter) are reported.
Time frame: Day 1 through 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acalabrutinib | Number of Participants With Treatment-emergent Atrial Fibrillation | 32 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Atrial Fibrillation | 49 Participants |
Secondary
Number of Participants With Treatment-emergent Infections Grade >= 3
Number of participants with treatment-emergent infections Grade \>=3 are reported.
Time frame: Day 1 through 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acalabrutinib | Number of Participants With Treatment-emergent Infections Grade >= 3 | 98 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Infections Grade >= 3 | 101 Participants |
Secondary
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.
Time frame: Day 1 through 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Absolute neutrophil count (decreased) | 124 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Haemoglobin (decreased) | 139 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Platelets (decreased) | 119 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Leukocytes (decreased) | 60 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Leukocytes (increased) | 68 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Absolute lymphocyte count (ALC) (decreased) | 66 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | ALC (increased) | 71 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Alanine aminotransferase (increased) | 73 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Albumin (decreased) | 31 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Alkaline phosphatase (increased) | 66 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Aspartate aminotransferase (increased) | 42 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Bilirubin (increased) | 46 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Calcium (decreased) | 56 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Calcium (increased) | 15 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Creatinine (increased) | 164 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Glucose (decreased) | 5 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Glucose (increased) | 21 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Phosphate (decreased) | 93 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Potassium (decreased) | 27 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Potassium (increased) | 62 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Sodium (decreased) | 26 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Sodium (increased) | 70 Participants |
| Acalabrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Urate (increased) | 70 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Bilirubin (increased) | 69 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Absolute neutrophil count (decreased) | 135 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Phosphate (decreased) | 74 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Haemoglobin (decreased) | 131 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Calcium (decreased) | 71 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Platelets (decreased) | 116 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Sodium (decreased) | 37 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Leukocytes (decreased) | 64 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Calcium (increased) | 11 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Leukocytes (increased) | 84 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Potassium (decreased) | 40 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Absolute lymphocyte count (ALC) (decreased) | 65 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Creatinine (increased) | 168 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | ALC (increased) | 72 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Urate (increased) | 96 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Alanine aminotransferase (increased) | 70 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Glucose (decreased) | 13 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Albumin (decreased) | 44 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Potassium (increased) | 52 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Alkaline phosphatase (increased) | 60 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Glucose (increased) | 23 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Aspartate aminotransferase (increased) | 58 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Laboratory Abnormalities | Sodium (increased) | 46 Participants |
Secondary
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.
Time frame: Day 1 through 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acalabrutinib | Number of Participants With Treatment-emergent Richter's Transformation | 13 Participants |
| Ibrutinib | Number of Participants With Treatment-emergent Richter's Transformation | 14 Participants |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)
Population: ITT population included all participants randomized and were analyzed according to the arm to which they were randomly assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acalabrutinib | Overall Survival (OS) | NA Months |
| Ibrutinib | Overall Survival (OS) | NA Months |
Secondary
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.
Time frame: Day 1 through 83.5 months (maximum observed duration)
Population: Safety population included all participants who received at least one dose of study drug and were analyzed as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acalabrutinib | Percentage of Participants With Lymphocytosis | 72.5 Percentage of participants |
| Ibrutinib | Percentage of Participants With Lymphocytosis | 74.3 Percentage of participants |