Chronic Lymphocytic Leukemia, Indolent Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma
Conditions
Keywords
phosphatidylinositol 3-kinase, Ofatumumab, indolent non-Hodgkin lymphoma (iNHL)
Brief summary
The primary objective of the study is to evaluate the safety of idelalisib in combination with an anti-CD20 monoclonal antibody (mAb), a chemotherapeutic agent, a mammalian target of rapamycin (mTOR) inhibitor, a protease inhibitor, an antiangiogenic agent, and/or an immunomodulatory agent in participants with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL).
Interventions
DRUGIdelalisib
Idelalisib tablet administered orally
DRUGRituximab
Rituximab administered intravenously
DRUGBendamustine
Bendamustine administered intravenously
DRUGOfatumumab
Ofatumumab administered intravenously
DRUGFludarabine
Fludarabine administered orally
DRUGEverolimus
Everolimus administered orally twice daily until disease progression
DRUGBortezomib
Bortezomib administered as a subcutaneous injection
DRUGChlorambucil
Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens.
DRUGLenalidomide
Lenalidomide administered orally
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥ 18 * Previously treated with relapsed or refractory disease (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen) * Disease status requirement: * For CLL patients, symptomatic disease that mandates treatment as defined by the International Workshop on Chronic Lymphocytic Lymphoma (IWCLL) 2008 criteria * For indolent NHL and MCL patients, measurable disease by CT scan defined as at least 1 lesion that measures \> 2 cm in a single dimension * WHO performance status of ≤ 2 * For men and women of child-bearing potential, willing to use adequate contraception (ie, latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study. * For Cohort 7 only: Women of child bearing potential must have 2 negative pregnancy tests prior to starting lenalidomide. * Able to provide written informed consent Key
Exclusion criteria
* Is not a good candidate to receive any of the drugs administered in the study for a given disease (idelalisib, bendamustine, rituximab, ofatumumab, fludarabine, everolimus, bortezomib, or chlorambucil), according to the clinical judgment of the investigator * Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1 over-expression (CLL patients only) * Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to the baseline disease status tests * Had treatment with a short course of corticosteroids for symptom relief within 1-week prior to the baseline disease status tests * Has had an allogeneic hematopoietic stem cell transplant * Has known active central nervous system involvement of the malignancy * Is pregnant or nursing * Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the investigator * Has absolute neutrophil count (ANC) \< 1000/µL, unless it is related to underlying CLL, MCL or indolent NHL, the latter documented by \> 50% infiltration of bone marrow by tumor cells * Has platelet count \< 75000/µL, unless it is related to underlying CLL, MCL, or iNHL, the latter documented by \> 50% infiltration of bone marrow by tumor cells * Has serum creatinine ≥ 2.0 mg/dL * For Cohort 7 only: Has creatinine clearance \< 60 mL/min * Has serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) for patients with iNHL or CLL; for patients with MCL, serum bilirubin ≥ 1.5 x upper limit of normal * Has serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ 2 x upper limit of normal * Has Child-Pugh Class B or C hepatic impairment * Has a positive test for HIV antibodies * Has active hepatitis B or C (confirmed by RNA test). Patients with serologic evidence of prior exposure are eligible. * Prior treatment with idelalisib Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Exposure to IDELA | First dose date up to 12 months | Duration of exposure to IDELA was summarized using descriptive statistics. |
| Toxicity of Administration of IDELA | First dose date up to 5 years | Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of IDELA (Cohort 7) | Predose, 1.5 hours postdose at Weeks 0, 5 and 13 | — |
| Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose | — |
| Overall Response Rate | Up to 5 years | Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR). The response definitions were based on the following standard criteria established for each indication: * CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008 * iNHL & MCL: Cheson, 2007 |
| Duration of Response | Up to 5 years | Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause. |
| Time to Response | Up to 5 years | Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR. |
| Plasma Concentration of IDELA (Cohort 4) | Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24 | — |
| Overall Survival | Up to 5 years | Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause. |
| Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24 | — |
| Plasma Concentration of Bendamustine | Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0 | — |
| Plasma Concentration of Everolimus | Predose, 1.5 hours postdose at Weeks 0 and 4 | — |
| Plasma Concentration of Lenalidomide | Predose, 1.5 hours postdose at Week 1 and predose at Week 5 | — |
| Progression-free Survival | Up to 5 years | Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause. The response definitions were based on the following standard criteria established for each indication: * CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008 * iNHL & MCL: Cheson, 2007 |
| Plasma Concentration of IDELA (Cohort 6) | Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24 | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United States. The first participant was screened on 25 March 2010. The last study visit occurred on 28 April 2015.
Pre-assignment details
277 participants were screened. Per prespecified analysis, participants were grouped by disease (chronic lymphocytic leukemia, indolent non-Hodgkin lymphoma, mantle cell lymphoma) and by treatment regimen (cohort).
Participants by arm
| Arm | Count |
|---|---|
| Idelalisib + Rituximab Participants with CLL and iNHL received treatments as follows:
Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2
Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2
Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2
Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m\^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 | 51 |
| Idelalisib + Bendamustine Participants with CLL and iNHL received treatments as follows:
Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 | 51 |
| Idelalisib + Everolimus Participants with MCL received treatments as follows:
Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle | 18 |
| Idelalisib + Bortezomib Participants with MCL received treatments as follows:
Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m\^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle | 18 |
| Idelalisib + Rituximab + Bendamustine Participants with CLL, iNHL and MCL received treatments as follows:
Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6
Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m\^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 | 33 |
| Idelalisib + Ofatumumab Participants with CLL received treatments as follows:
Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) | 21 |
| Idelalisib + Fludarabine Participants with CLL received treatments as follows:
Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m\^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 | 12 |
| Idelalisib + Chlorambucil Participants with CLL received treatments as follows:
Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m\^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 | 15 |
| Idelalisib + Rituximab + Chlorambucil Participants with CLL received treatments as follows:
Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m\^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 | 15 |
| Idelalisib + Rituximab + Lenalidomide Participants with CLL and iNHL received treatments as follows:
Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m\^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m\^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m\^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles | 7 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 9 | 7 | 5 | 6 | 3 | 3 | 0 | 2 | 2 |
| Overall Study | Concomitant Medication Prohibited | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 1 | 5 | 3 | 3 | 1 | 3 | 0 | 0 | 3 | 1 |
| Overall Study | Disease Progression | 7 | 4 | 3 | 5 | 3 | 3 | 2 | 1 | 0 | 0 |
| Overall Study | Investigator Request | 2 | 2 | 0 | 0 | 3 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 3 | 5 | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Patient Non-compliance | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrew Consent | 1 | 1 | 1 | 1 | 2 | 1 | 0 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Idelalisib + Rituximab | Idelalisib + Bendamustine | Idelalisib + Everolimus | Idelalisib + Bortezomib | Idelalisib + Rituximab + Bendamustine | Idelalisib + Ofatumumab | Idelalisib + Fludarabine | Idelalisib + Chlorambucil | Idelalisib + Rituximab + Chlorambucil | Idelalisib + Rituximab + Lenalidomide | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 10.1 | 61 years STANDARD_DEVIATION 11.2 | 69 years STANDARD_DEVIATION 7.1 | 72 years STANDARD_DEVIATION 6 | 60 years STANDARD_DEVIATION 8.3 | 66 years STANDARD_DEVIATION 9.7 | 69 years STANDARD_DEVIATION 7.1 | 63 years STANDARD_DEVIATION 7.8 | 68 years STANDARD_DEVIATION 10 | 61 years STANDARD_DEVIATION 8.3 | 64 years STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized Asian | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 51 Participants | 49 Participants | 18 Participants | 17 Participants | 31 Participants | 21 Participants | 11 Participants | 14 Participants | 15 Participants | 7 Participants | 234 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 42 Participants | 45 Participants | 16 Participants | 14 Participants | 29 Participants | 20 Participants | 8 Participants | 14 Participants | 15 Participants | 6 Participants | 209 Participants |
| Sex: Female, Male Female | 16 Participants | 21 Participants | 7 Participants | 3 Participants | 12 Participants | 6 Participants | 4 Participants | 1 Participants | 4 Participants | 2 Participants | 76 Participants |
| Sex: Female, Male Male | 35 Participants | 30 Participants | 11 Participants | 15 Participants | 21 Participants | 15 Participants | 8 Participants | 14 Participants | 11 Participants | 5 Participants | 165 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 51 | 6 / 51 | 4 / 18 | 3 / 18 | 1 / 33 | 4 / 21 | 2 / 12 | 0 / 15 | 3 / 15 | 2 / 7 |
| other Total, other adverse events | 51 / 51 | 51 / 51 | 18 / 18 | 15 / 18 | 33 / 33 | 21 / 21 | 12 / 12 | 15 / 15 | 15 / 15 | 7 / 7 |
| serious Total, serious adverse events | 20 / 51 | 37 / 51 | 14 / 18 | 6 / 18 | 17 / 33 | 12 / 21 | 9 / 12 | 9 / 15 | 8 / 15 | 5 / 7 |
Outcome results
Primary
Duration of Exposure to IDELA
Duration of exposure to IDELA was summarized using descriptive statistics.
Time frame: First dose date up to 12 months
Population: The ITT analysis set included participants who received at least 1 dose of study drug (idelalisib or combination drugs). Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idelalisib + Rituximab | Duration of Exposure to IDELA | 8.1 months | Standard Deviation 3.74 |
| Idelalisib + Bendamustine | Duration of Exposure to IDELA | 7.6 months | Standard Deviation 3.96 |
| Idelalisib + Everolimus | Duration of Exposure to IDELA | 4.2 months | Standard Deviation 3.92 |
| Idelalisib + Bortezomib | Duration of Exposure to IDELA | 5.1 months | Standard Deviation 3.9 |
| Idelalisib + Rituximab + Bendamustine | Duration of Exposure to IDELA | 8.0 months | Standard Deviation 4.16 |
| Idelalisib + Ofatumumab | Duration of Exposure to IDELA | 8.3 months | Standard Deviation 4.03 |
| Idelalisib + Fludarabine | Duration of Exposure to IDELA | 8.9 months | Standard Deviation 3.57 |
| Idelalisib + Chlorambucil | Duration of Exposure to IDELA | 8.8 months | Standard Deviation 3.76 |
| Idelalisib + Rituximab + Chlorambucil | Duration of Exposure to IDELA | 8.7 months | Standard Deviation 3.01 |
| Idelalisib + Rituximab + Lenalidomide | Duration of Exposure to IDELA | 7.7 months | Standard Deviation 4.78 |
Primary
Toxicity of Administration of IDELA
Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02
Time frame: First dose date up to 5 years
Population: Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Idelalisib + Rituximab | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Bendamustine | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Everolimus | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Bortezomib | Toxicity of Administration of IDELA | 83.33 percentage of participants |
| Idelalisib + Rituximab + Bendamustine | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Ofatumumab | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Fludarabine | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Chlorambucil | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Rituximab + Chlorambucil | Toxicity of Administration of IDELA | 100.0 percentage of participants |
| Idelalisib + Rituximab + Lenalidomide | Toxicity of Administration of IDELA | 100.0 percentage of participants |
Secondary
Duration of Response
Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.
Time frame: Up to 5 years
Population: Participants in the ITT analysis set with available data were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Idelalisib + Rituximab | Duration of Response | NA months |
| Idelalisib + Bendamustine | Duration of Response | NA months |
| Idelalisib + Everolimus | Duration of Response | 5.6 months |
| Idelalisib + Bortezomib | Duration of Response | 9.3 months |
| Idelalisib + Rituximab + Bendamustine | Duration of Response | NA months |
| Idelalisib + Ofatumumab | Duration of Response | NA months |
| Idelalisib + Fludarabine | Duration of Response | NA months |
| Idelalisib + Chlorambucil | Duration of Response | NA months |
| Idelalisib + Rituximab + Chlorambucil | Duration of Response | NA months |
| Idelalisib + Rituximab + Lenalidomide | Duration of Response | NA months |
Secondary
Overall Response Rate
Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR). The response definitions were based on the following standard criteria established for each indication: * CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008 * iNHL & MCL: Cheson, 2007
Time frame: Up to 5 years
Population: Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Idelalisib + Rituximab | Overall Response Rate | 78.4 percentage of participants |
| Idelalisib + Bendamustine | Overall Response Rate | 84.3 percentage of participants |
| Idelalisib + Everolimus | Overall Response Rate | 44.4 percentage of participants |
| Idelalisib + Bortezomib | Overall Response Rate | 61.1 percentage of participants |
| Idelalisib + Rituximab + Bendamustine | Overall Response Rate | 81.8 percentage of participants |
| Idelalisib + Ofatumumab | Overall Response Rate | 71.4 percentage of participants |
| Idelalisib + Fludarabine | Overall Response Rate | 91.7 percentage of participants |
| Idelalisib + Chlorambucil | Overall Response Rate | 66.7 percentage of participants |
| Idelalisib + Rituximab + Chlorambucil | Overall Response Rate | 93.3 percentage of participants |
| Idelalisib + Rituximab + Lenalidomide | Overall Response Rate | 71.4 percentage of participants |
Secondary
Overall Survival
Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.
Time frame: Up to 5 years
Population: Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Idelalisib + Rituximab | Overall Survival | NA months |
| Idelalisib + Bendamustine | Overall Survival | NA months |
| Idelalisib + Everolimus | Overall Survival | NA months |
| Idelalisib + Bortezomib | Overall Survival | NA months |
| Idelalisib + Rituximab + Bendamustine | Overall Survival | NA months |
| Idelalisib + Ofatumumab | Overall Survival | NA months |
| Idelalisib + Fludarabine | Overall Survival | NA months |
| Idelalisib + Chlorambucil | Overall Survival | NA months |
| Idelalisib + Rituximab + Chlorambucil | Overall Survival | NA months |
| Idelalisib + Rituximab + Lenalidomide | Overall Survival | NA months |
Secondary
Plasma Concentration of Bendamustine
Time frame: Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0
Population: Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohorts 1b, 2b, 3a, 3b, 3f, 3g, 4b, 5c who received bendamustine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | Pre-dose (Week 0) | NA ng/mL | — |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 0.25 hr post-dose (Week 0) | 3484.1 ng/mL | Standard Deviation 2617.17 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 0.5 hr post-dose (Week 0) | 4694.7 ng/mL | Standard Deviation 3570.78 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 0.75 hr post-dose (Week 0) | 3433.2 ng/mL | Standard Deviation 2991.15 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 1.0 hr post-dose (Week 0) | 2847.2 ng/mL | Standard Deviation 2462.9 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 1.25 hr post-dose (Week 0) | 1916.4 ng/mL | Standard Deviation 1551.5 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 1.5 hr post-dose (Week 0) | 1211.2 ng/mL | Standard Deviation 1093.74 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 2.0 hr post-dose (Week 0) | 514.0 ng/mL | Standard Deviation 489.76 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 3.0 hr post-dose (Week 0) | 463.4 ng/mL | Standard Deviation 1529.3 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 4.0 hr post-dose (Week 0) | 78.5 ng/mL | Standard Deviation 238.3 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 5.0 hr post-dose (Week 0) | 15.3 ng/mL | Standard Deviation 36.79 |
| Idelalisib + Rituximab | Plasma Concentration of Bendamustine | 6.0 hr post-dose (Week 0) | 4.4 ng/mL | Standard Deviation 6.58 |
Secondary
Plasma Concentration of Everolimus
Time frame: Predose, 1.5 hours postdose at Weeks 0 and 4
Population: Participants in the PK analysis set with available data were analyzed. Data were summarized for participants in Cohort 5a who received everolimus.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Plasma Concentration of Everolimus | Pre-dose (Week 0) | NA ng/mL | — |
| Idelalisib + Rituximab | Plasma Concentration of Everolimus | 1.5 hr post-dose (Week 0) | 93.0 ng/mL | Standard Deviation 63.5 |
| Idelalisib + Rituximab | Plasma Concentration of Everolimus | Pre-dose (Week 4) | 3.0 ng/mL | Standard Deviation 3.79 |
| Idelalisib + Rituximab | Plasma Concentration of Everolimus | 1.5 hr post-dose (Week 4) | 56.3 ng/mL | Standard Deviation 67.48 |
Secondary
Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)
Time frame: Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24
Population: The pharmacokinetic (PK) analysis set included data from participants in the ITT analysis set who had the necessary baseline and on-study measurements to provide interpretable results for the specific parameters of interest. Per prespecified analysis, data were summarized for participants in Cohort 1a 1b, who received idelalisib 100 mg and for participants in Cohorts 2a, 2b, 3a, 3b, 3c, 3d, 3e, 3f, 3g 5a, 5b, and 5c who received idelalisib 150 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 12) | 361.9 ng/mL | Standard Deviation 580.7 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 3.0 hr post-dose (Week 0) | 1001.0 ng/mL | Standard Deviation 633.99 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.0 hr post-dose (Week 0) | 1022.4 ng/mL | Standard Deviation 652.92 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 4) | 1297.2 ng/mL | Standard Deviation 681.43 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 4.0 hr post-dose (Week 0) | 788.4 ng/mL | Standard Deviation 629.67 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 0.5 hr post-dose (Week 0) | 437.6 ng/mL | Standard Deviation 380.08 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 4) | 416.5 ng/mL | Standard Deviation 636.01 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 6.0 hr post-dose (Week 0) | 523.7 ng/mL | Standard Deviation 418.8 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 12) | 1309.5 ng/mL | Standard Deviation 750.5 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 0) | 1434.0 ng/mL | Standard Deviation 835.25 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 24) | 1061.6 ng/mL | Standard Deviation 567.9 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 0) | 0.4 ng/mL | Standard Deviation 2.16 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 2.0 hr post-dose (Week 0) | 1282.7 ng/mL | Standard Deviation 789.24 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 24) | 369.9 ng/mL | Standard Deviation 461.67 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 12) | 351.4 ng/mL | Standard Deviation 389.78 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 0) | 68.8 ng/mL | Standard Deviation 396.94 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 0.5 hr post-dose (Week 0) | 1231.4 ng/mL | Standard Deviation 1238.2 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.0 hr post-dose (Week 0) | 1789.3 ng/mL | Standard Deviation 1162.31 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 0) | 2017.3 ng/mL | Standard Deviation 1241.96 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 2.0 hr post-dose (Week 0) | 1732.8 ng/mL | Standard Deviation 744.87 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 3.0 hr post-dose (Week 0) | 1296.1 ng/mL | Standard Deviation 509.8 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 4.0 hr post-dose (Week 0) | 910.0 ng/mL | Standard Deviation 420.79 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 6.0 hr post-dose (Week 0) | 486.0 ng/mL | Standard Deviation 276.75 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 4) | 364.1 ng/mL | Standard Deviation 341.84 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 4) | 1808.1 ng/mL | Standard Deviation 931.67 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 12) | 1883.0 ng/mL | Standard Deviation 973.26 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 24) | 419.7 ng/mL | Standard Deviation 359.03 |
| Idelalisib + Bendamustine | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 24) | 1840.1 ng/mL | Standard Deviation 1035.91 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 24) | 549.1 ng/mL | Standard Deviation 622.95 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 4) | 1877.9 ng/mL | Standard Deviation 859.74 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 2.0 hr post-dose (Week 0) | 1400.0 ng/mL | — |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 0) | 1564.7 ng/mL | Standard Deviation 983.46 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 12) | 433.9 ng/mL | Standard Deviation 529.79 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.0 hr post-dose (Week 0) | 1600.0 ng/mL | — |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 0) | 0.0 ng/mL | Standard Deviation 0 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 12) | 1426.8 ng/mL | Standard Deviation 917.02 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 0.5 hr post-dose (Week 0) | 1380.0 ng/mL | — |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 6.0 hr post-dose (Week 0) | 517.0 ng/mL | — |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 4.0 hr post-dose (Week 0) | 795.0 ng/mL | — |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 1.5 hr post-dose (Week 24) | 885.6 ng/mL | Standard Deviation 568.81 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | Pre-dose (Week 4) | 408.0 ng/mL | Standard Deviation 699.35 |
| Idelalisib + Everolimus | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) | 3.0 hr post-dose (Week 0) | 1170.0 ng/mL | — |
Secondary
Plasma Concentration of IDELA (Cohort 4)
Time frame: Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24
Population: Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 4a, 4b who received idelalisib 150mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 4.0 hr post-dose (Week 4) | 547.0 ng/mL | Standard Deviation 158.39 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 6.0 hr post-dose (Week 4) | 524.0 ng/mL | Standard Deviation 404.47 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | Pre-dose (Week 0) | 0.0 ng/mL | Standard Deviation 0 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | Pre-dose (Week 4) | 0.0 ng/mL | Standard Deviation 0 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 0.5 hr post-dose (Week 4) | 1119.5 ng/mL | Standard Deviation 1513.99 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 1.0 hr post-dose (Week 4) | 994.5 ng/mL | Standard Deviation 601.75 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 1.5 hr post-dose (Week 4) | 1758.2 ng/mL | Standard Deviation 1414.07 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 2.0 hr post-dose (Week 4) | 737.0 ng/mL | Standard Deviation 108.89 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 3.0 hr post-dose (Week 4) | 605.0 ng/mL | Standard Deviation 18.38 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | Pre-dose (Week 12) | 401.9 ng/mL | Standard Deviation 344.93 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 1.5 hr post-dose (Week 12) | 2018.2 ng/mL | Standard Deviation 1703.98 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | Pre-dose (Week 24) | 752.5 ng/mL | Standard Deviation 967.91 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 4) | 1.5 hr post-dose (Week 24) | 2251.1 ng/mL | Standard Deviation 1744.44 |
Secondary
Plasma Concentration of IDELA (Cohort 6)
Time frame: Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24
Population: Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 6a, 6b who received idelalisib 150mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | Pre-dose (Week 0) | 0.0 ng/mL | Standard Deviation 0 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | 1.5 hr post-dose (Week 0) | 1930.7 ng/mL | Standard Deviation 1220.87 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | Pre-dose (Week 4) | 530.8 ng/mL | Standard Deviation 563.59 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | 1.5 hr post-dose (Week 4) | 1869.8 ng/mL | Standard Deviation 1001.39 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | Pre-dose (Week 12) | 677.9 ng/mL | Standard Deviation 940.94 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | 1.5 hr post-dose (Week 12) | 1733.0 ng/mL | Standard Deviation 941.94 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | Pre-dose (Week 24) | 346.8 ng/mL | Standard Deviation 377.84 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 6) | 1.5 hr post-dose (Week 24) | 1710.7 ng/mL | Standard Deviation 1235.08 |
Secondary
Plasma Concentration of IDELA (Cohort 7)
Time frame: Predose, 1.5 hours postdose at Weeks 0, 5 and 13
Population: Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 7a, 7b, 7c who received idelalisib 150mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 7) | Pre-dose (Week 13) | 354.8 ng/mL | Standard Deviation 278.62 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 7) | 1.5 hr post-dose (Week 13) | 592.7 ng/mL | Standard Deviation 597.52 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 7) | Pre-dose (Week 0) | NA ng/mL | — |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 7) | 1.5 hr post-dose (Week 0) | 1603.1 ng/mL | Standard Deviation 1196.78 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 7) | Pre-dose (Week 5) | 20.7 ng/mL | Standard Deviation 50.13 |
| Idelalisib + Rituximab | Plasma Concentration of IDELA (Cohort 7) | 1.5 hr post-dose (Week 5) | 1621.3 ng/mL | Standard Deviation 663.8 |
Secondary
Plasma Concentration of Lenalidomide
Time frame: Predose, 1.5 hours postdose at Week 1 and predose at Week 5
Population: Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 7a, 7b, 7c who received lenalidomide.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Plasma Concentration of Lenalidomide | Pre-dose (Week 5) | NA ng/mL | — |
| Idelalisib + Rituximab | Plasma Concentration of Lenalidomide | Pre-dose (Week 1) | NA ng/mL | — |
| Idelalisib + Rituximab | Plasma Concentration of Lenalidomide | 1.5 hr post-dose (Week 1) | 51.6 ng/mL | Standard Deviation 31.77 |
Secondary
Progression-free Survival
Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause. The response definitions were based on the following standard criteria established for each indication: * CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008 * iNHL & MCL: Cheson, 2007
Time frame: Up to 5 years
Population: Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Idelalisib + Rituximab | Progression-free Survival | NA months |
| Idelalisib + Bendamustine | Progression-free Survival | NA months |
| Idelalisib + Everolimus | Progression-free Survival | 4.3 months |
| Idelalisib + Bortezomib | Progression-free Survival | 8.1 months |
| Idelalisib + Rituximab + Bendamustine | Progression-free Survival | NA months |
| Idelalisib + Ofatumumab | Progression-free Survival | NA months |
| Idelalisib + Fludarabine | Progression-free Survival | NA months |
| Idelalisib + Chlorambucil | Progression-free Survival | NA months |
| Idelalisib + Rituximab + Chlorambucil | Progression-free Survival | NA months |
| Idelalisib + Rituximab + Lenalidomide | Progression-free Survival | NA months |
Secondary
Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)
Time frame: pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose
Population: Participants with CLL or iNHL from the PK Analysis Set in Cohorts 1, 2, 3, and 4 who participated in the PK substudy were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 1a, 1b who received idelalisib 100mg and Cohorts 2a, 2b, 3a, 3c, 3d, 3e, 3f, 3g, 4a, 4b who received idelalisib 150 mg in the PK substudy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | Pre-dose | 1.5 ng/mL | Standard Deviation 4.01 |
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 0.5 hr post-dose | 437.6 ng/mL | Standard Deviation 380.08 |
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 1.0 hr post-dose | 1022.4 ng/mL | Standard Deviation 652.92 |
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 1.5 hr post-dose | 1264.7 ng/mL | Standard Deviation 868.41 |
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 2.0 hr post-dose | 1282.7 ng/mL | Standard Deviation 789.24 |
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 3.0 hr post-dose | 1001.0 ng/mL | Standard Deviation 633.99 |
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 4.0 hr post-dose | 788.4 ng/mL | Standard Deviation 629.67 |
| Idelalisib + Rituximab | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 6.0 hr post-dose | 523.7 ng/mL | Standard Deviation 418.8 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 6.0 hr post-dose | 489.3 ng/mL | Standard Deviation 277.82 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | Pre-dose | 0.0 ng/mL | Standard Deviation 0 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 2.0 hr post-dose | 1646.2 ng/mL | Standard Deviation 766.31 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 0.5 hr post-dose | 1222.1 ng/mL | Standard Deviation 1224.95 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 4.0 hr post-dose | 879.8 ng/mL | Standard Deviation 416.25 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 1.0 hr post-dose | 1723.1 ng/mL | Standard Deviation 1140 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 3.0 hr post-dose | 1238.5 ng/mL | Standard Deviation 524.77 |
| Idelalisib + Bendamustine | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) | 1.5 hr post-dose | 1599.2 ng/mL | Standard Deviation 746.58 |
Secondary
Time to Response
Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.
Time frame: Up to 5 years
Population: Participants in the ITT analysis set with available data were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Idelalisib + Rituximab | Time to Response | 1.9 months |
| Idelalisib + Bendamustine | Time to Response | 1.9 months |
| Idelalisib + Everolimus | Time to Response | 1.9 months |
| Idelalisib + Bortezomib | Time to Response | 1.9 months |
| Idelalisib + Rituximab + Bendamustine | Time to Response | 1.9 months |
| Idelalisib + Ofatumumab | Time to Response | 1.9 months |
| Idelalisib + Fludarabine | Time to Response | 1.9 months |
| Idelalisib + Chlorambucil | Time to Response | 1.9 months |
| Idelalisib + Rituximab + Chlorambucil | Time to Response | 1.9 months |
| Idelalisib + Rituximab + Lenalidomide | Time to Response | 3.0 months |