Refractory Diffuse Large B-Cell Lymphoma, Relapsed Diffuse Large B-Cell Lymphoma
Conditions
Keywords
DLBCL
Brief summary
This Phase 1b/2 study is designed to assess the safety and efficacy of ibrutinib in combination with lenalidomide and rituximab in subjects with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not eligible for transplant.
Detailed description
Phase 1b: In the dose escalation portion of the study, various cohorts with escalating doses of lenalidomide may be explored, using the 3+3+3 principle for dose determination. Phase 2: This will be conducted as an international, multicenter, open-label study. Eligible subjects will receive ibrutinib, lenalidomide and rituximab.
Interventions
DRUGIbrutinib
DRUGLenalidomide
DRUGRituximab
Sponsors
Janssen Research & Development, LLC
Celgene Corporation
Pharmacyclics LLC.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed relapsed/ refractory DLBCL * Must have previously received first line treatment regimen * Must be ineligible for high dose therapy/ stem cell transplantation * Measurable disease sites on computed tomography (CT) scan (\>1.5 cm in longest dimension) * prothrombin time/international normalized ratio (PT/INR) \< 1.5 x upper limit of normal (ULN) and partial thromboplastin time (PTT; activated partial thromboplastin time \[aPTT\]) \<1.5 x ULN * Men and women ≥18 years of age * Eastern Cooperative Oncology Group (ECOG) \< 2 * Adequate hepatic and renal function * Adequate hematologic function
Exclusion criteria
* Medically apparent central nervous system lymphoma or leptomeningeal disease * History of allogeneic stem-cell (or other organ) transplantation * Any chemotherapy, external beam radiation therapy, or anticancer antibodies within 2 weeks * Radio- or toxin-immunoconjugates within 10 weeks * Concurrent enrollment in another therapeutic investigational study or have previously taken ibrutinib and/or lenalidomide.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) | Estimated median time on study in Phase 1b was 59.6 months. | The dose levels of lenalidomide were explored, and dose escalation of lenalidomide followed the 3+3+3 dose escalation schema. A Dose Level Review Committee evaluated safety data following completion of each dose observation period of the Phase 1b portion. |
| Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | From first dose of study drug up to 30 days after last dose of study drug. Phase 1b median duration of ibrutinib exposure was 4.4 months; median duration of lenalidomide exposure was 4.4 months; median total number of doses of rituximab received was 4.0. | An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization \> 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death. |
| Phase 2: Overall Response Rate (ORR) | Estimated median time on study in Phase 2 was 35.0 months. | The ORR was defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014), as assessed by the investigator in response-evaluable population. The 95% confidence interval (CI) was calculated using the exact method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Duration of Response (DOR) | Estimated median time on study in Phase 2 was 35.0 months. | DOR is defined as the time from the date of the first documented response (CR or PR) to the first documented evidence of disease progression (PD) according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause. For participants who had achieved an overall response but did not die or progress at the time of analysis, DOR was censored on the date of the last adequate post-baseline disease assessment, or on the date of the first occurrence of response (CR or PR) if there was no disease assessment afterwards. 2-sided 95% CI is estimated by Kaplan-Meier method. |
| Phase 2: Progression Free Survival (PFS) | Estimated median time on study in Phase 2 was 35.0 months. | PFS is defined as the time from the date of the first dose of study drug to confirmed PD according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause, whichever occurred first. For participants without disease progression or death, PFS data was censored at the date of the last tumor assessment. 2 sided 95% CI is estimated by Kaplan-Meier method. |
| Phase 1b: ORR | Estimated median time on study in Phase 1b was 59.6 months. | The ORR was defined as the percentage of participants who achieve either a PR or CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease and PR=regression of measurable disease and no new sites. The 95% CI was calculated using the exact method. |
| Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | From first dose of study drug up to 30 days after last dose of study drug. Phase 2 median duration of ibrutinib exposure was 4.9 months; median duration of lenalidomide exposure was 4.7 months; median total number of doses of rituximab received was 5.0. | An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization \> 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death. |
| Phase 2: Overall Survival (OS) | Estimated median time on study in Phase 2 was 35.0 months. | OS is defined as the time from the date of the first dose of study drug to the date of death due to any cause. For participants not known to have died at or prior to the database lock date, OS data was censored at the date last known alive. Participants who withdrew consent prior to study closure were censored on the date of the consent withdrawal. 2-sided 95% CI was estimated by Kaplan-Meier method. |
| Phase 1b: Complete Response (CR) Rate | Estimated median time on Phase 1b study was 59.6 months. | The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease, as assessed by the Investigator. |
| Phase 2: CR Rate | Estimated median time on study in Phase 2 was 35.0 months. | The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (see Cheson, 2014 for detailed criteria) in response-evaluable population, as assessed by the Investigator. |
Countries
Belgium, Germany, United Kingdom, United States
Participant flow
Recruitment details
All participants had relapsed/refractory diffuse large B-cell lymphoma (DLBCL). In the Phase 1b portion of the study, all subtypes of DLBCL and participants with transformed disease were enrolled. In the Phase 2 portion of the study, only participants with non-germinal-center B-cell-like (non-GCB) DLBCL were enrolled.
Pre-assignment details
In the Phase 1b portion of this study, different dose levels of lenalidomide were explored, and dose escalation of lenalidomide followed the 3+3+3 dose escalation schema. A total of 138 participants enrolled in the study; however, 4 participants exited the study without receiving any treatment, and are not presented in any data table.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1) Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 15 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles. | 12 |
| Phase 1: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 10 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered intravenously (IV) on Day 1 of each 28-day cycle for 6 cycles. | 7 |
| Phase 1: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 15 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles. | 9 |
| Phase 1: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 20 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles. | 9 |
| Phase 1: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 25 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles. | 8 |
| Phase 2: Enrolled at Lenalidomide Dose 20 mg Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 20 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles. | 55 |
| Phase 2: Enrolled at Lenalidomide Dose 25 mg Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 25 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles. | 34 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 6 | 7 | 5 | 6 | 4 | 32 | 22 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other, Not Specified | 0 | 0 | 1 | 0 | 1 | 7 | 8 |
| Overall Study | Study Closure by Sponsor | 3 | 0 | 2 | 2 | 2 | 12 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 1 | 1 | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Phase 1: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1) | Phase 1: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 2: Enrolled at Lenalidomide Dose 20 mg | Phase 2: Enrolled at Lenalidomide Dose 25 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 13.13 | 58.4 years STANDARD_DEVIATION 7.63 | 65.3 years STANDARD_DEVIATION 13.44 | 66.0 years STANDARD_DEVIATION 8.63 | 62.9 years STANDARD_DEVIATION 14.23 | 63.1 years STANDARD_DEVIATION 11.75 | 64.9 years STANDARD_DEVIATION 12.52 | 63.9 years STANDARD_DEVIATION 11.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 4 Participants | 8 Participants | 9 Participants | 8 Participants | 55 Participants | 29 Participants | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Declined to Answer/Unknown | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiple Races | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 5 Participants | 8 Participants | 9 Participants | 7 Participants | 51 Participants | 30 Participants | 121 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 3 Participants | 23 Participants | 14 Participants | 57 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 32 Participants | 20 Participants | 77 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 12 | 7 / 7 | 5 / 9 | 7 / 9 | 5 / 8 | 33 / 55 | 22 / 34 |
| other Total, other adverse events | 12 / 12 | 7 / 7 | 9 / 9 | 9 / 9 | 8 / 8 | 54 / 55 | 34 / 34 |
| serious Total, serious adverse events | 4 / 12 | 6 / 7 | 7 / 9 | 5 / 9 | 6 / 8 | 32 / 55 | 25 / 34 |
Outcome results
Primary
Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization \> 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death.
Time frame: From first dose of study drug up to 30 days after last dose of study drug. Phase 1b median duration of ibrutinib exposure was 4.4 months; median duration of lenalidomide exposure was 4.4 months; median total number of doses of rituximab received was 4.0.
Population: All-Treated Analysis Population (Phase 1): participants who received any dose of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 3 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 4 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 2 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 4 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 6 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 0 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 6 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 6 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 10 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 0 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 12 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 12 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 11 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 0 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 10 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 0 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 12 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 4 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 9 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 4 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 6 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 0 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 3 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 1 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 12 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 4 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 4 Participants |
| All Phase 1b Participants | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 0 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 0 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 0 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 2 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 0 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 1 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 8 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 3 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 3 Participants |
Primary
Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
The dose levels of lenalidomide were explored, and dose escalation of lenalidomide followed the 3+3+3 dose escalation schema. A Dose Level Review Committee evaluated safety data following completion of each dose observation period of the Phase 1b portion.
Time frame: Estimated median time on study in Phase 1b was 59.6 months.
Population: All-Treated Analysis Population (Phase 1b): participants who received any dose of study drug(s).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase 1b Participants | Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) | 20 mg |
Primary
Phase 2: Overall Response Rate (ORR)
The ORR was defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014), as assessed by the investigator in response-evaluable population. The 95% confidence interval (CI) was calculated using the exact method.
Time frame: Estimated median time on study in Phase 2 was 35.0 months.
Population: Response-Evaluable Population: participants who had measurable disease at baseline and had at least 1 adequate post-treatment disease assessment by the investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase 1b Participants | Phase 2: Overall Response Rate (ORR) | 52.8 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Overall Response Rate (ORR) | 43.8 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Overall Response Rate (ORR) | 49.4 percentage of participants |
Secondary
Phase 1b: Complete Response (CR) Rate
The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease, as assessed by the Investigator.
Time frame: Estimated median time on Phase 1b study was 59.6 months.
Population: Response-Evaluable Population: participants who had measurable disease at baseline and had at least 1 adequate post-treatment disease assessment by the investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase 1b Participants | Phase 1b: Complete Response (CR) Rate | 33.3 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: Complete Response (CR) Rate | 0 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: Complete Response (CR) Rate | 42.9 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: Complete Response (CR) Rate | 11.1 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: Complete Response (CR) Rate | 50.0 percentage of participants |
| Phase 1b Total: Enrolled at Lenalidomide Dose 10 to 25 mg (All Dose Levels) | Phase 1b: Complete Response (CR) Rate | 27.5 percentage of participants |
Secondary
Phase 1b: ORR
The ORR was defined as the percentage of participants who achieve either a PR or CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease and PR=regression of measurable disease and no new sites. The 95% CI was calculated using the exact method.
Time frame: Estimated median time on study in Phase 1b was 59.6 months.
Population: Response-Evaluable Population: participants who had measurable disease at baseline and had at least 1 adequate post-treatment disease assessment by the investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase 1b Participants | Phase 1b: ORR | 44.4 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 1b: ORR | 0 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 1b: ORR | 71.4 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | Phase 1b: ORR | 22.2 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | Phase 1b: ORR | 75.0 percentage of participants |
| Phase 1b Total: Enrolled at Lenalidomide Dose 10 to 25 mg (All Dose Levels) | Phase 1b: ORR | 42.5 percentage of participants |
Secondary
Phase 2: CR Rate
The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (see Cheson, 2014 for detailed criteria) in response-evaluable population, as assessed by the Investigator.
Time frame: Estimated median time on study in Phase 2 was 35.0 months.
Population: Response-Evaluable Population: participants who had measurable disease at baseline and had at least 1 adequate post-treatment disease assessment by the investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase 1b Participants | Phase 2: CR Rate | 32.1 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: CR Rate | 21.9 percentage of participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: CR Rate | 28.2 percentage of participants |
Secondary
Phase 2: Duration of Response (DOR)
DOR is defined as the time from the date of the first documented response (CR or PR) to the first documented evidence of disease progression (PD) according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause. For participants who had achieved an overall response but did not die or progress at the time of analysis, DOR was censored on the date of the last adequate post-baseline disease assessment, or on the date of the first occurrence of response (CR or PR) if there was no disease assessment afterwards. 2-sided 95% CI is estimated by Kaplan-Meier method.
Time frame: Estimated median time on study in Phase 2 was 35.0 months.
Population: All-Treated Analysis Population (Phase 2): participants who received any dose of study drug(s). Participant who achieved Overall Response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Phase 1b Participants | Phase 2: Duration of Response (DOR) | 38.3 months |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Duration of Response (DOR) | 28.6 months |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Duration of Response (DOR) | 38.3 months |
Secondary
Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization \> 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death.
Time frame: From first dose of study drug up to 30 days after last dose of study drug. Phase 2 median duration of ibrutinib exposure was 4.9 months; median duration of lenalidomide exposure was 4.7 months; median total number of doses of rituximab received was 5.0.
Population: All-Treated Analysis Population (Phase 2): participants who received any dose of study drug(s).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 18 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 41 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 11 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 23 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 51 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 11 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 12 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 14 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 10 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 21 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 50 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 37 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 40 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 55 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 38 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 16 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 36 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 4 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 29 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 51 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 52 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 32 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 40 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 8 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 6 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 37 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 16 Participants |
| All Phase 1b Participants | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 11 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 12 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 34 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 30 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 33 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 25 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 32 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 24 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 32 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 25 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 25 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 13 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 14 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 14 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 29 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 28 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 26 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 7 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 25 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 21 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 12 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 6 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 10 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 5 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 4 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Ibrutinib Dose | 16 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related TEAE | 62 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Study Drug-Related TEAE | 85 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Lenalidomide Dose | 18 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Lenalidomide-Related TEAE | 65 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE | 89 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Rituximab Dose | 10 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related TEAE | 83 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Lenalidomide-Related Serious TEAE | 26 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Serious TEAE | 57 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Ibrutinib-Related TEAE | 60 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 TEAE | 81 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Serious TEAE | 50 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related TEAE | 82 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Fatal TEAE | 12 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Any Study Drug | 69 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Treatment-Related Serious TEAE | 28 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Ibrutinib | 66 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Lenalidomide | 35 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >=3 Study Drug-Related TEAE | 66 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Lenalidomide | 63 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Ibrutinib | 21 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Delay of Rituximab | 16 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Dose Reduction of Any Study Drug | 37 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Rituximab-Related Serious TEAE | 9 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any TEAE Leading to Discontinuation of Any Study Drug | 18 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Grade >= 3 Rituximab-Related TEAE | 31 Participants |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs | Any Ibrutinib-Related Serious TEAE | 26 Participants |
Secondary
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of the first dose of study drug to the date of death due to any cause. For participants not known to have died at or prior to the database lock date, OS data was censored at the date last known alive. Participants who withdrew consent prior to study closure were censored on the date of the consent withdrawal. 2-sided 95% CI was estimated by Kaplan-Meier method.
Time frame: Estimated median time on study in Phase 2 was 35.0 months.
Population: All-Treated Analysis Population (Phase 2): participants who received any dose of study drug(s).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Phase 1b Participants | Phase 2: Overall Survival (OS) | 14.7 months |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Overall Survival (OS) | 11.6 months |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Overall Survival (OS) | 14.2 months |
Secondary
Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from the date of the first dose of study drug to confirmed PD according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause, whichever occurred first. For participants without disease progression or death, PFS data was censored at the date of the last tumor assessment. 2 sided 95% CI is estimated by Kaplan-Meier method.
Time frame: Estimated median time on study in Phase 2 was 35.0 months.
Population: All-Treated Analysis Population (Phase 2): participants who received any dose of study drug(s).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Phase 1b Participants | Phase 2: Progression Free Survival (PFS) | 5.4 months |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | Phase 2: Progression Free Survival (PFS) | 4.7 months |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | Phase 2: Progression Free Survival (PFS) | 5.4 months |