Lymphoma, Mantle-Cell
Conditions
Brief summary
The purpose of this study is to provide continued access to treatment for participants who continue to benefit from treatment.
Detailed description
Mantle cell lymphoma (MCL) is an uncommon and incurable clinicopathologic subtype of B-cell non-Hodgkin Lymphoma (NHL). Ibrutinib is a first-in-class potent, orally administered, covalently-binding small molecule inhibitor of Bruton's tyrosine kinase (BTKi) for the treatment of B-cell malignancies and chronic graft-versus-host disease. The primary hypothesis of the study is to provide continued access to treatment for participants who continue to benefit from treatment. The study will include a screening phase (up to 30 days prior to randomization), a treatment phase (from randomization until study treatment discontinuation). safety assessments include adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, vital signs, electrocardiogram (ECG), physical examination. The Phase 2 exploratory objectives and endpoints of characterization of pharmacokinetic and pharmacodynamic of ibrutinib may continue to be evaluated using blood samples already collected. The total duration of the study will be up to 2 years 1 month.
Interventions
DRUGIbrutinib
Ibrutinib capsules will be administered orally.
DRUGLenalidomide
Lenalidomide capsules will be administered orally.
DRUGRituximab
Rituximab will be administered IV.
DRUGBortezomib
Bortezomib will be administered either intravenously or subcutaneously.
Sponsors
Pharmacyclics LLC.
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 1 prior treatment regimen for mantle cell lymphoma (MCL) excluding inhibitor of Bruton's tyrosine kinase (BTKi) * Documented disease progression or relapse following the last anti-MCL treatment * At least 1 measurable site of disease on cross-sectional imaging that is greater than or equal to (\>=) 2.0 centimeters (cm) in the longest diameter and measurable in 2 perpendicular dimensions per computed tomography (CT) * Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
Exclusion criteria
* Prior therapy with ibrutinib or other BTK inhibitor * Prior treatment with both lenalidomide and bortezomib. Prior treatment with only 1 of these therapies is allowed * Major surgery within 4 weeks of randomization * Concurrent enrollment in another therapeutic investigational study * Known central nervous system lymphoma * History of stroke or intracranial hemorrhage within 6 months prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months) | An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. All TEAEs including serious and non-serious events were reported in this outcome measure. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Monotherapy Arm | From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. All TEAEs included serious and non-serious events were reported in this outcome measure. |
| Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Arms A1, A2, A3 and B | From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. TEAEs were graded according to NCI-CTCAE v5.0 as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences and Grade 5- Death related to AE. Number of participants with grade 3 or higher TEAEs (including serious and non-serious events) were reported in this outcome measure. |
| Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Monotherapy Arm | From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. TEAEs were graded according to NCI-CTCAE v5.0 as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences and Grade 5- Death related to AE. Number of participants with grade 3 or higher TEAEs (including serious and non-serious events) were reported in this outcome measure. |
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B | From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TESAEs was defined as SAEs occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. |
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Monotherapy Arm | From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TESAEs was defined as SAEs occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. |
| Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | From start of treatment (Day 1) up to 30 days after last dose of study drug (up to 12 months) | Number of participants with clinical abnormalities in hematology laboratory parameters were reported. Hematology parameters included: Activated partial thromboplastin time (aPTT), hemoglobin, neutrophil count, white blood cell (WBC) count, lymphocyte count, platelet count and prothrombin international normalized ratio (INR). Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported. |
| Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug (up to 6 months) | Number of participants with clinical abnormalities in hematology laboratory parameters were reported. Hematology parameters included: Activated partial thromboplastin time (aPTT), hemoglobin, neutrophil count, white blood cell (WBC) count, lymphocyte count, platelet count and prothrombin international normalized ratio (INR). Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported. |
| Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | From start of treatment (Day 1) up to 30 days after last dose of study drug (up to 12 months) | Number of participants with clinical abnormalities in chemistry laboratory parameters were reported. Chemistry parameters included: sodium, aspartate aminotransferase (AST), potassium, alanine aminotransferase (ALT), creatinine, total bilirubin (BL), alkaline phosphatase, albumin, and calcium. Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported. |
| Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug (up to 6 months) | Number of participants with clinical abnormalities in chemistry laboratory parameters were reported. Chemistry parameters included: sodium, aspartate aminotransferase (AST), potassium, alanine aminotransferase (ALT), creatinine, total bilirubin, alkaline phosphatase, albumin, and calcium. Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported. |
Countries
Brazil, Czechia, Greece, India, Malaysia, Poland, Puerto Rico, Romania, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye)
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 parts: Phase 2 and Phase 3. However, due to early termination of enrollment, no participants were enrolled on the Phase 3 part of the study. Hence, the results were only presented for Phase 2 part. Participants with relapsed or refractory mantle cell lymphoma were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 Participants received ibrutinib 560 milligrams (mg; 4 capsules of 140 mg) orally once daily (QD) in each 28-day treatment cycle starting from Cycle 1 Day 1 until disease progression or unacceptable toxicity. Participants also received rituximab 375 milligrams per meter square (mg/m\^2) intravenous (IV) infusion on Day 1 of each 28-day treatment cycle from Cycles 1 to 6. After implementation of Protocol Amendment 1 (dated 08 June 2023), all participants were given the option either to continue with the randomized treatment arm or switch to ibrutinib monotherapy to receive ibrutinib 560 mg capsules orally QD (unless the dose was previously reduced) until the investigator determined that the participant was no longer benefiting from treatment (disease progression or unacceptable toxicity had occurred), the participant withdrew consent, alternative access to study treatment was available and feasible, or until the end of the study, whichever occurred earlier. | 10 |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 Participants received ibrutinib 420 mg (3 capsules of 140 mg) orally QD in each 28-day treatment cycle starting from Cycle 1 Day 1 until disease progression or unacceptable toxicity. Participants also received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day treatment cycle from Cycles 1 to 6. After implementation of Protocol Amendment 1 (dated 08 June 2023), all participants were given the option either to continue with the randomized treatment arm or switch to ibrutinib monotherapy to receive ibrutinib 560 mg capsules orally QD (unless the dose was previously reduced) until the investigator determined that the participant was no longer benefiting from treatment (disease progression or unacceptable toxicity had occurred), the participant withdrew consent, alternative access to study treatment was available and feasible, or until the end of the study, whichever occurred earlier. | 9 |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 Participants received ibrutinib 140mg (1 capsule of 140mg) orally twice daily (BID) in each 28-day treatment cycle starting from Cycle 1 Day 1 until disease progression or unacceptable toxicity. Participants also received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day treatment cycle from Cycles 1 to 6. After implementation of Protocol Amendment 1 (dated 08 June 2023), all participants were given the option either to continue with the randomized treatment arm or switch to ibrutinib monotherapy to receive ibrutinib 560 mg capsules orally QD (unless the dose was previously reduced) until the investigator determined that the participant was no longer benefiting from treatment (disease progression or unacceptable toxicity had occurred), the participant withdrew consent, alternative access to study treatment was available and feasible, or until the end of the study, whichever occurred earlier. | 8 |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 Participants received lenalidomide 20 mg (or 10 mg if creatinine clearance \[CrCl\] was 30 to less than \[\<\] 60 milliliters per minute \[mL/min\]) capsule orally QD on Days 1 through 21 in each 28-day treatment cycle starting from Cycle 1 Day 1 until disease progression or unacceptable toxicity. Participants also received rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day treatment cycle from Cycles 1 to 6. After implementation of Protocol Amendment 1 (dated 08 June 2023), all participants were given the option either to continue with the randomized treatment arm or switch to ibrutinib monotherapy to receive ibrutinib 560 mg capsules orally QD until the investigator determined that the participant was no longer benefiting from treatment (disease progression or unacceptable toxicity had occurred), the participant withdrew consent, alternative access to study treatment was available and feasible, or until the end of the study, whichever occurred earlier. | 9 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 68.9 Years STANDARD_DEVIATION 8.08 | 64.6 Years STANDARD_DEVIATION 10.35 | 66.5 Years STANDARD_DEVIATION 7.23 | 64.6 Years STANDARD_DEVIATION 7.6 | 66.2 Years STANDARD_DEVIATION 8.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 7 Participants | 6 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 6 Participants | 5 Participants | 22 Participants |
| Region of Enrollment BRAZIL | 2 Participants | 2 Participants | 5 Participants | 3 Participants | 12 Participants |
| Region of Enrollment CZECH REPUBLIC | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment GREECE | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment MALAYSIA | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Region of Enrollment POLAND | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants |
| Region of Enrollment SPAIN | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Region of Enrollment TAIWAN | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment THAILAND | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Region of Enrollment TURKEY | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 6 Participants | 8 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 10 | 0 / 9 | 1 / 8 | 2 / 9 | 0 / 9 |
| other Total, other adverse events | 10 / 10 | 7 / 9 | 8 / 8 | 8 / 9 | 4 / 9 |
| serious Total, serious adverse events | 4 / 10 | 3 / 9 | 2 / 8 | 5 / 9 | 1 / 9 |
Outcome results
Primary
Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B
Number of participants with clinical abnormalities in chemistry laboratory parameters were reported. Chemistry parameters included: sodium, aspartate aminotransferase (AST), potassium, alanine aminotransferase (ALT), creatinine, total bilirubin (BL), alkaline phosphatase, albumin, and calcium. Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.
Time frame: From start of treatment (Day 1) up to 30 days after last dose of study drug (up to 12 months)
Population: Safety population was defined as all randomized participants of arms A1, A2, A3 and B who received at least 1 dose of any ibrutinib dosage level or control drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 0 | 9 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 0 | 5 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 0 | 10 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Alkaline Phosphatase (AP) Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 3 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 1 | 4 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 1 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 2 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 2 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 3 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 1 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 4 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Bilirubin (BL) Increased Grade 0 | 7 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 1 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 1 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 0 | 7 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 1 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 2 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 1 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 0 | 6 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 2 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 2 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 2 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 0 | 7 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 3 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 0 | 10 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AP Increased Grade 1 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 1 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 0 | 7 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 1 | 4 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 0 | 5 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 1 | 3 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 1 | 2 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Alkaline Phosphatase (AP) Increased Grade 0 | 8 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 2 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AP Increased Grade 1 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 1 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 0 | 9 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 0 | 9 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 1 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 0 | 7 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 0 | 8 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 1 | 2 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 2 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 2 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 1 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 0 | 7 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 1 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 0 | 9 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 0 | 8 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 1 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 2 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Bilirubin (BL) Increased Grade 0 | 7 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 4 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 1 | 2 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 0 | 6 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 2 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 2 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 0 | 9 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 0 | 7 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 0 | 6 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 2 | 2 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 4 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 0 | 7 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Alkaline Phosphatase (AP) Increased Grade 0 | 5 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 2 | 1 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 1 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 0 | 5 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 1 | 3 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 0 | 8 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AP Increased Grade 1 | 3 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 1 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 0 | 8 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 1 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Bilirubin (BL) Increased Grade 0 | 7 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 0 | 8 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 1 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 2 | 1 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 0 | 4 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 0 | 6 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 1 | 2 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 2 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 0 | 8 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 1 | 4 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 1 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 0 | 4 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 1 | 2 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 2 | 2 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 2 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 1 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 0 | 6 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 1 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | ALT Increased Grade 3 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 0 | 7 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 1 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Albumin Decreased Grade 2 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Alkaline Phosphatase (AP) Increased Grade 0 | 7 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AP Increased Grade 1 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 0 | 6 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 1 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | AST Increased Grade 3 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Bilirubin (BL) Increased Grade 0 | 8 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 1 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 2 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | BL Increased Grade 3 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 0 | 6 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 1 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Decreased Grade 2 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Calcium Corrected Increased Grade 0 | 8 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 1 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 0 | 6 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 1 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Creatinine Increased Grade 2 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 0 | 9 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 2 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Decreased Grade 4 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 0 | 9 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Potassium Increased Grade 2 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 0 | 8 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Decreased Grade 1 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B | Sodium Increased Grade 0 | 8 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm
Number of participants with clinical abnormalities in chemistry laboratory parameters were reported. Chemistry parameters included: sodium, aspartate aminotransferase (AST), potassium, alanine aminotransferase (ALT), creatinine, total bilirubin, alkaline phosphatase, albumin, and calcium. Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.
Time frame: From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug (up to 6 months)
Population: Monotherapy population was defined as participants who were randomized to Arms A2, A3 and B and later switched to ibrutinib 560 mg QD monotherapy. Here 'N' (overall number of participants analyzed) refers to the number of participants evaluable for this outcome measure and 'n' (number analyzed) refers to number of participants analyzed for each specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | ALT Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Albumin Decreased Grade 0 | 6 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Albumin Decreased Grade 1 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Alkaline Phosphatase Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | AST Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Bilirubin Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Calcium Corrected Decreased Grade 0 | 7 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Calcium Corrected Decreased Grade 1 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Calcium Corrected Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Creatinine Increased Grade 0 | 7 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Creatinine Increased Grade 1 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Potassium Decreased Grade 0 | 7 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Potassium Decreased Grade 2 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Potassium Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Sodium Decreased Grade 0 | 5 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Sodium Decreased Grade 1 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm | Sodium Increased Grade 0 | 8 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B
Number of participants with clinical abnormalities in hematology laboratory parameters were reported. Hematology parameters included: Activated partial thromboplastin time (aPTT), hemoglobin, neutrophil count, white blood cell (WBC) count, lymphocyte count, platelet count and prothrombin international normalized ratio (INR). Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.
Time frame: From start of treatment (Day 1) up to 30 days after last dose of study drug (up to 12 months)
Population: Safety population was defined as all randomized participants of arms A1, A2, A3 and B who received at least 1 dose of any ibrutinib dosage level or control drug. Here, 'n' (number analyzed) signifies the participants analyzed for each specified parameter and n=0 signifies that there was no evaluable participant for specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 3 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 2 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 3 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 1 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 0 | 4 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 4 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 2 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 3 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 3 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | aPTT Prolonged Grade 1 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 2 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 2 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 1 | 5 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 3 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 3 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 0 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Prothrombin INR Increased Grade 0 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Increased Grade 0 | 10 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 0 | 10 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 4 | 0 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 3 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 0 | 4 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 1 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 2 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 1 | 4 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 1 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 0 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 0 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 4 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 2 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 4 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 2 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 0 | 2 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 1 | 6 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 2 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Increased Grade 0 | 9 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 0 | 5 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 1 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 2 | 4 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 4 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 0 | 8 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 0 | 7 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 1 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 2 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 3 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 4 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 0 | 2 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 1 | 5 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 2 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 4 | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 0 | 4 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 1 | 5 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 2 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 3 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 4 | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 0 | 9 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 2 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 3 | 1 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 0 | 5 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 1 | 2 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 4 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 0 | 8 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 1 | 3 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 0 | 7 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 2 | 1 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 4 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 2 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 0 | 7 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 3 | 4 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 2 | 1 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 1 | 1 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 4 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 2 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 1 | 4 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 0 | 5 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 0 | 4 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Increased Grade 0 | 8 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 3 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 2 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 1 | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 4 | 1 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 0 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 2 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 2 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 3 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 1 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 3 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 4 | 4 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 0 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 0 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 3 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 1 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 2 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Increased Grade 0 | 9 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 4 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 3 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 0 | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Platelet Count Decreased Grade 4 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 3 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 0 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 2 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 1 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Increased Grade 0 | 8 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 0 | 6 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 4 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 2 | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Increased Grade 3 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Lymphocyte Count Decreased Grade 3 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | WBC Decreased Grade 2 | 3 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 0 | 1 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Hemoglobin Decreased Grade 1 | 5 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B | Neutrophil Count Decreased Grade 1 | 1 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm
Number of participants with clinical abnormalities in hematology laboratory parameters were reported. Hematology parameters included: Activated partial thromboplastin time (aPTT), hemoglobin, neutrophil count, white blood cell (WBC) count, lymphocyte count, platelet count and prothrombin international normalized ratio (INR). Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.
Time frame: From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug (up to 6 months)
Population: Monotherapy population was defined as participants who were randomized to Arms A2, A3 and B and later switched to ibrutinib 560 mg QD monotherapy. Here 'N' (overall number of participants analyzed) refers to the number of participants evaluable for this outcome measure and 'n' (number analyzed) refers to number of participants analyzed for each specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | aPTT Prolonged Grade 0 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Hemoglobin Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Hemoglobin Decreased Grade 0 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Hemoglobin Decreased Grade 1 | 5 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Hemoglobin Decreased Grade 2 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Lymphocyte Count Decreased Grade 0 | 5 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Lymphocyte Count Decreased Grade 1 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Lymphocyte Count Decreased Grade 2 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Lymphocyte Count Decreased Grade 4 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Lymphocyte Count Increased Grade 0 | 8 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Neutrophil Count Decreased Grade 0 | 6 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Neutrophil Count Decreased Grade 1 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Neutrophil Count Decreased Grade 2 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Platelet Count Decreased Grade 0 | 2 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Platelet Count Decreased Grade 1 | 6 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | Prothrombin INR Increased Grade 0 | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | WBC Decreased Grade 0 | 5 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | WBC Decreased Grade 1 | 3 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm | WBC Increased Grade 0 | 8 Participants |
Primary
Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Arms A1, A2, A3 and B
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. TEAEs were graded according to NCI-CTCAE v5.0 as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences and Grade 5- Death related to AE. Number of participants with grade 3 or higher TEAEs (including serious and non-serious events) were reported in this outcome measure.
Time frame: From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months)
Population: Safety population was defined as all randomized participants of arms A1, A2, A3 and B who received at least 1 dose of any ibrutinib dosage level or control drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Arms A1, A2, A3 and B | 7 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Arms A1, A2, A3 and B | 3 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Arms A1, A2, A3 and B | 5 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Arms A1, A2, A3 and B | 8 Participants |
Primary
Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Monotherapy Arm
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. TEAEs were graded according to NCI-CTCAE v5.0 as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences and Grade 5- Death related to AE. Number of participants with grade 3 or higher TEAEs (including serious and non-serious events) were reported in this outcome measure.
Time frame: From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months)
Population: Monotherapy population was defined as participants who were randomized to Arms A2, A3 and B and later switched to ibrutinib 560 mg QD monotherapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Monotherapy Arm | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B
An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. All TEAEs including serious and non-serious events were reported in this outcome measure.
Time frame: From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months)
Population: Safety population was defined as all randomized participants of arms A1, A2, A3 and B who received at least 1 dose of any ibrutinib dosage level or control drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Ibrutinib/Lenalidomide | 1 Participants |
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Rituximab | 0 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Rituximab | 1 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Ibrutinib/Lenalidomide | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Ibrutinib/Lenalidomide | 0 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Rituximab | 0 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Ibrutinib/Lenalidomide | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B | Discontinuation of Treatment Rituximab | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Monotherapy Arm
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. All TEAEs included serious and non-serious events were reported in this outcome measure.
Time frame: From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months)
Population: Monotherapy population was defined as participants who were randomized to Arms A2, A3 and B and later switched to ibrutinib 560 mg QD monotherapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Monotherapy Arm | 1 Participants |
Primary
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TESAEs was defined as SAEs occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first.
Time frame: From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months)
Population: Safety population was defined as all randomized participants of arms A1, A2, A3 and B who received at least 1 dose of any ibrutinib dosage level or control drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B | 4 Participants |
| Arm A2: Ibrutinib 420 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B | 3 Participants |
| Arm A3: Ibrutinib 140 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B | 2 Participants |
| Arm B: Lenalidomide 20 mg (or 10 mg if CrCl Was 30 to <60 mL/Min) + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B | 5 Participants |
Primary
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Monotherapy Arm
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TESAEs was defined as SAEs occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first.
Time frame: From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months)
Population: Monotherapy population was defined as participants who were randomized to Arms A2, A3 and B and later switched to ibrutinib 560 mg QD monotherapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1: Ibrutinib 560 mg + Rituximab 375 mg/m^2 | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Monotherapy Arm | 1 Participants |