Follicular Lymphoma
Conditions
Brief summary
The primary objective of this study is to establish a safe and effective dosing regimen of idelalisib in participants with relapsed or refractory follicular lymphoma (FL) who have no other therapeutic options.
Interventions
DRUGIdelalisib
Idelalisib tablet administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Double-blind: Prior to protocol amendment 5; Open-label: Participants enrolled as of protocol amendment 5
Intervention model description
As of protocol amendment 5, the Idelalisib 100 mg arm is closed to enrollment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically confirmed diagnosis of B-cell follicular lymphoma (FL), and grade limited to 1, 2, or 3a based on criteria established by the World Health Organization (WHO) 2008 classification of tumors of hematopoietic and lymphoid tissues * Relapsed or refractory FL and have received at least 2 lines of prior therapy for FL and have no other available therapeutic options. Note: Rituximab maintenance is not routinely considered a separate line of therapy when it is given as part of the prior rituximab-containing regimen given over a number of cycles followed by maintenance. Rituximab monotherapy may be considered a separate line of therapy when disease relapse occurs between the initiation of rituximab monotherapy and the preceding line of therapy. If there are any ambiguities about eligibility, the site should consult with the medical monitor. * Ann-Arbor Stage 2 (non-contiguous), 3, or 4 disease per Lugano Classification Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures ≥ 1.5 cm in the longest dimension (LD) and ≥ 1.0 cm in the longest perpendicular dimension (LPD) as assessed by positron emission tomography-computed tomography (PET-CT), computed tomography (CT) or magnetic resonance imaging (MRI) * Required baseline central laboratory data in protocol. * For female individuals of childbearing potential and male individuals of reproductive potential, willingness to use a protocol- recommended method of contraception * Lactating females must agree to discontinue nursing * Willing and able to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions including mandatory prophylaxis for Pneumocystis jirovecii pneumonia (PJP) Key
Exclusion criteria
* History of lymphoid malignancy other than FL (eg, diffuse large B-cell lymphoma) * Known history of, or clinically apparent, central nervous system (CNS) lymphoma or leptomeningeal lymphoma. * Known presence of intermediate- or high-grade myelodysplastic syndrome. * Known history of serious allergic reaction including anaphylaxis or Stevens- Johnson syndrome/ toxic epidermal necrolysis * History of a non-lymphoid malignancy except for protocol allowed exceptions * Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment * Known history of drug-induced liver injury, chronic active hepatitis B virus (HBV), chronic active hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, portal hypertension, primary biliary cirrhosis, or ongoing extrahepatic obstruction caused by cholelithiasis * History of or ongoing drug-induced pneumonitis * History of or ongoing inflammatory bowel disease * Known human immunodeficiency virus (HIV) infection * History of prior allogeneic bone marrow progenitor cell or solid organ transplantation * Ongoing immunosuppressive therapy, including systemic corticosteroids (\> 10 mg prednisone or equivalent/day) with the exception of the use of topical, enteric, or inhaled corticosteroids as therapy for comorbid conditions and systemic steroids for autoimmune anemia and/or thrombocytopenia * Concurrent participation in another therapeutic clinical trial * Prior treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors * Cytomegalovirus (CMV): Ongoing infection, treatment, or specifically CMV antiviral prophylaxis within 28 days prior to the screening visits CMV test Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Randomization up to end of treatment (maximum duration: 73.5 months) | ORR was defined as percentage of participants who achieve a partial response (PR) or complete response (CR). PR criteria: No evidence of new disease, a ≥50% decrease from baseline in sum of products of diameters (SPD) of index lesions, no increase in non-index disease, no increase in liver/spleen size and no new liver/spleen enlargement. Persistence of bone marrow involvement in a participant who meets other criteria for CR based on the disappearance of all nodal and extra-nodal masses. CR criteria: No evidence of new disease, regression of all index nodal lesions to normal size (≤1.5 cm in longest dimension (LD) for large nodes and ≤1.0 cm in LD, ≤1.0 cm in longest perpendicular dimension (LPD) for small nodes), regression to normal of all nodal non-index disease, disappearance of all detectable extra-nodal index and non-index disease, normal spleen and liver size, no new liver/spleen enlargement, morphologically negative bone marrow. |
| Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs) | First dose date up to 30 days after last dose of study drug (maximum 64.6 months) | TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | First dose date up to 30 days after last dose of study drug (maximum 64.6 months) | TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. TEAEs severity was graded according to the NCI CTCAE version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants are counted at the highest AE grade experienced. |
| Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | First dose date up to 30 days after last dose of study drug (maximum 64.6 months) | Treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last study drug dose plus 30 days. Laboratory abnormalities included hematology and serum chemistry parameters. Clinically significant laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for severity as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening). The number of participants with any post-baseline abnormal laboratory value in Grade 1-4 categories are reported. |
| Time to Onset of Adverse Events of Interest (AEIs) | First dose date up to 30 days after last dose of study drug (maximum 64.6 months) | Time to onset of AEIs is defined as the interval (in months) from the start of idelalisib treatment to the first documentation of start of AEI. AEIs included grade ≥ 3 diarrhea/colitis, rash, febrile neutropenia, infection, and any grade of: Pneumonitis, bowel perforation, progressive multifocal leukoencephalopathy (PML), Pneumocystis jirovecii pneumonia (PJP), cytomegalovirus (CMV) infection, and organizing pneumonia. |
| Duration of Response (DOR) | From first documentation of CR or PR until PD or death from any cause (maximum duration: 73.5 months) | DOR: interval from first documentation of CR/PR to earlier of first documentation of disease progression (PD) by independent review committee (IRC)/death from any cause. PR:No evidence of new disease,≥50% decrease from baseline in SPD of index lesions,no increase in non-index disease, no increase in liver/spleen size,no new liver/spleen enlargement; Persistence of bone marrow involvement in participant who meets other CR criteria. CR: No evidence of new disease,regression of all index nodal lesions to normal size (large nodes:≤1.5 cm in LD;small nodes:≤1.0 cm in LD,≤1.0 cm in LPD), regression to normal of all nodal non-index disease,disappearance of all detectable extra-nodal index,non-index disease,normal spleen and liver size, no new liver/spleen enlargement; PD: New node of \>1.5 cm or \>1.0 to ≤1.5 cm in LD, \>1.0 cm in LPD, new/unequivocal reappearance of resolved extra-nodal lesion,new non-index disease,increase by 50% in SPD of index lesions,LD of individual node/extra-nodal mass. |
| Overall Survival (OS) | Randomization up to death from any cause (maximum duration: 73.5 months) | OS is defined as the interval (in months) from randomization to death from any cause. |
| Trough Plasma Concentration of Idelalisib | Predose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48 | — |
| Peak Plasma Concentration of Idelalisib | 1.5 hours postdose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48 | — |
| Progression-Free Survival (PFS) | Randomization up to PD or death from any cause (maximum duration: 73.5 months) | PFS is defined as the interval (in months) from randomization to the earlier of the first documentation of PD by IRC or death from any cause. PD criteria: New node of \>1.5 cm or \>1.0 cm to ≤1.5 cm in LD, \>1.0 cm in LPD, new/unequivocal reappearance of resolved extra-nodal lesion, new non-index disease, increase by 50% in SPD of index lesions, LD of individual node/extra-nodal mass. |
| Overall Response Rate (ORR) by Week 24 | First dose date up to Week 24 | ORR by Week 24 is defined as the percentage of participants who achieve a PR or CR by Week 24. PR criteria: No evidence of new disease, a 50% decrease from baseline in SPD of index lesions, no increase in non-index disease, no increase in liver/spleen size and no new liver/spleen enlargement. CR criteria: No evidence of new disease, regression of all index nodal lesions to normal size (≤1.5 cm in LD for large nodes and ≤1.0 cm in LD, ≤1.0 cm in LPD for small nodes), regression to normal of all nodal non-index disease, disappearance of all detectable extra-nodal index and non-index disease, normal spleen and liver size, no new liver/spleen enlargement, morphologically negative bone marrow. |
Countries
Australia, Canada, Czechia, France, Israel, Italy, Poland, Romania, Spain, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in Australia, Canada, Europe, Israel, and the United Kingdom.
Pre-assignment details
145 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Idelalisib 150 mg BID Participants received idelalisib 150 mg tablets, orally, BID, continuously for up to maximum 33.5 months. | 47 |
| Idelalisib 100 mg BID Participants received idelalisib 100 mg tablets, orally, BID, continuously for up to maximum 63.6 months. | 27 |
| Idelalisib 150 mg BID INT Participants received idelalisib 150 mg tablets, orally, BID for 21 days and 7 days off-treatment (INT dosing schedule) in each 28-day cycle for up to maximum of 24.6 months. | 21 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 7 | 0 | 5 |
| Overall Study | Enrolled but Never Treated | 0 | 0 | 1 |
| Overall Study | Initiation of Non-study Specific Anti-cancer Therapy in the Absence of Progression | 1 | 2 | 1 |
| Overall Study | Investigator's Discretion | 17 | 11 | 2 |
| Overall Study | Non-compliance With Study Drug | 1 | 0 | 0 |
| Overall Study | Progressive Disease | 11 | 7 | 6 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 6 | 4 | 7 |
| Overall Study | Withdrew Consent | 4 | 2 | 0 |
Baseline characteristics
| Characteristic | Idelalisib 150 mg BID | Total | Idelalisib 150 mg BID INT | Idelalisib 100 mg BID |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 27 Participants | 50 Participants | 10 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 45 Participants | 11 Participants | 14 Participants |
| Age, Continuous | 65 years STANDARD_DEVIATION 13 | 64 years STANDARD_DEVIATION 12.8 | 63 years STANDARD_DEVIATION 11.6 | 62 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 85 Participants | 17 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other or More Than One Race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 4 Participants | 7 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 42 Participants | 85 Participants | 18 Participants | 25 Participants |
| Region of Enrollment Australia | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Canada | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Czechia | 4 Participants | 8 Participants | 1 Participants | 3 Participants |
| Region of Enrollment France | 5 Participants | 9 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Israel | 4 Participants | 4 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Italy | 10 Participants | 19 Participants | 4 Participants | 5 Participants |
| Region of Enrollment Poland | 8 Participants | 18 Participants | 4 Participants | 6 Participants |
| Region of Enrollment Romania | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Spain | 8 Participants | 18 Participants | 6 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 15 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 23 Participants | 44 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 24 Participants | 51 Participants | 13 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 20 / 47 | 12 / 27 | 6 / 22 |
| other Total, other adverse events | 44 / 47 | 24 / 27 | 16 / 21 |
| serious Total, serious adverse events | 31 / 47 | 19 / 27 | 11 / 21 |
Outcome results
Primary
Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced.
Time frame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Population: Safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Idelalisib 150 mg BID | Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs) | 15 Participants |
| Idelalisib 100 mg BID | Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs) | 12 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Grade 4 or Higher Treatment-Emergent Adverse Events (TEAEs) | 8 Participants |
Primary
Overall Response Rate (ORR)
ORR was defined as percentage of participants who achieve a partial response (PR) or complete response (CR). PR criteria: No evidence of new disease, a ≥50% decrease from baseline in sum of products of diameters (SPD) of index lesions, no increase in non-index disease, no increase in liver/spleen size and no new liver/spleen enlargement. Persistence of bone marrow involvement in a participant who meets other criteria for CR based on the disappearance of all nodal and extra-nodal masses. CR criteria: No evidence of new disease, regression of all index nodal lesions to normal size (≤1.5 cm in longest dimension (LD) for large nodes and ≤1.0 cm in LD, ≤1.0 cm in longest perpendicular dimension (LPD) for small nodes), regression to normal of all nodal non-index disease, disappearance of all detectable extra-nodal index and non-index disease, normal spleen and liver size, no new liver/spleen enlargement, morphologically negative bone marrow.
Time frame: Randomization up to end of treatment (maximum duration: 73.5 months)
Population: Intent-to-Treat (ITT) analysis set included all participants who were randomized regardless of whether they received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Idelalisib 150 mg BID | Overall Response Rate (ORR) | 38.3 percentage of participants |
| Idelalisib 100 mg BID | Overall Response Rate (ORR) | 44.4 percentage of participants |
| Idelalisib 150 mg BID INT | Overall Response Rate (ORR) | 40.9 percentage of participants |
Secondary
Duration of Response (DOR)
DOR: interval from first documentation of CR/PR to earlier of first documentation of disease progression (PD) by independent review committee (IRC)/death from any cause. PR:No evidence of new disease,≥50% decrease from baseline in SPD of index lesions,no increase in non-index disease, no increase in liver/spleen size,no new liver/spleen enlargement; Persistence of bone marrow involvement in participant who meets other CR criteria. CR: No evidence of new disease,regression of all index nodal lesions to normal size (large nodes:≤1.5 cm in LD;small nodes:≤1.0 cm in LD,≤1.0 cm in LPD), regression to normal of all nodal non-index disease,disappearance of all detectable extra-nodal index,non-index disease,normal spleen and liver size, no new liver/spleen enlargement; PD: New node of \>1.5 cm or \>1.0 to ≤1.5 cm in LD, \>1.0 cm in LPD, new/unequivocal reappearance of resolved extra-nodal lesion,new non-index disease,increase by 50% in SPD of index lesions,LD of individual node/extra-nodal mass.
Time frame: From first documentation of CR or PR until PD or death from any cause (maximum duration: 73.5 months)
Population: Participants in the ITT analysis set who achieved CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Idelalisib 150 mg BID | Duration of Response (DOR) | 27.1 months |
| Idelalisib 100 mg BID | Duration of Response (DOR) | 18.0 months |
| Idelalisib 150 mg BID INT | Duration of Response (DOR) | 5.7 months |
Secondary
Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib
TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. TEAEs severity was graded according to the NCI CTCAE version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants are counted at the highest AE grade experienced.
Time frame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Population: Participants in the safety analysis set were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Idelalisib 150 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Serious TEAEs | 31 Participants |
| Idelalisib 150 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Grade 3 or Higher TEAEs | 41 Participants |
| Idelalisib 150 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | TEAEs Leading to Discontinuation of Idelalisib | 28 Participants |
| Idelalisib 150 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Idelalisib-related TEAEs | 38 Participants |
| Idelalisib 150 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | TEAEs Leading to Interruption of Idelalisib | 32 Participants |
| Idelalisib 150 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Any TEAE | 45 Participants |
| Idelalisib 100 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | TEAEs Leading to Interruption of Idelalisib | 18 Participants |
| Idelalisib 100 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Any TEAE | 26 Participants |
| Idelalisib 100 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | TEAEs Leading to Discontinuation of Idelalisib | 13 Participants |
| Idelalisib 100 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Idelalisib-related TEAEs | 25 Participants |
| Idelalisib 100 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Grade 3 or Higher TEAEs | 25 Participants |
| Idelalisib 100 mg BID | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Serious TEAEs | 19 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | TEAEs Leading to Discontinuation of Idelalisib | 4 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Any TEAE | 19 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Grade 3 or Higher TEAEs | 12 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Serious TEAEs | 11 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | Idelalisib-related TEAEs | 11 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Any TEAE, Grade 3 or Higher TEAEs, Serious TEAEs, Idelalisib-related TEAEs, TEAEs Leading to Interruption or Discontinuation of Idelalisib | TEAEs Leading to Interruption of Idelalisib | 6 Participants |
Secondary
Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last study drug dose plus 30 days. Laboratory abnormalities included hematology and serum chemistry parameters. Clinically significant laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for severity as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening). The number of participants with any post-baseline abnormal laboratory value in Grade 1-4 categories are reported.
Time frame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Population: Participants in the safety analysis set with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 3 | 15 Participants |
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 4 | 6 Participants |
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 1 | 7 Participants |
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 2 | 12 Participants |
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 1 | 9 Participants |
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 2 | 17 Participants |
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 3 | 10 Participants |
| Idelalisib 150 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 4 | 7 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 1 | 5 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 3 | 11 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 2 | 7 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 1 | 5 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 2 | 8 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 3 | 11 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 4 | 3 Participants |
| Idelalisib 100 mg BID | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 4 | 3 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 1 | 2 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 4 | 2 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 3 | 5 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Hematology: Grade 2 | 5 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 3 | 6 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 2 | 4 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 1 | 8 Participants |
| Idelalisib 150 mg BID INT | Number of Participants With Clinically Significant Treatment-Emergent Laboratory Abnormalities | Serum Chemistry: Grade 4 | 1 Participants |
Secondary
Overall Response Rate (ORR) by Week 24
ORR by Week 24 is defined as the percentage of participants who achieve a PR or CR by Week 24. PR criteria: No evidence of new disease, a 50% decrease from baseline in SPD of index lesions, no increase in non-index disease, no increase in liver/spleen size and no new liver/spleen enlargement. CR criteria: No evidence of new disease, regression of all index nodal lesions to normal size (≤1.5 cm in LD for large nodes and ≤1.0 cm in LD, ≤1.0 cm in LPD for small nodes), regression to normal of all nodal non-index disease, disappearance of all detectable extra-nodal index and non-index disease, normal spleen and liver size, no new liver/spleen enlargement, morphologically negative bone marrow.
Time frame: First dose date up to Week 24
Population: Participants in the ITT analysis set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Idelalisib 150 mg BID | Overall Response Rate (ORR) by Week 24 | 36.2 percentage of participants |
| Idelalisib 100 mg BID | Overall Response Rate (ORR) by Week 24 | 33.3 percentage of participants |
| Idelalisib 150 mg BID INT | Overall Response Rate (ORR) by Week 24 | 27.3 percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the interval (in months) from randomization to death from any cause.
Time frame: Randomization up to death from any cause (maximum duration: 73.5 months)
Population: Participants in the ITT analysis set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Idelalisib 150 mg BID | Overall Survival (OS) | 28.7 months |
| Idelalisib 100 mg BID | Overall Survival (OS) | NA months |
| Idelalisib 150 mg BID INT | Overall Survival (OS) | NA months |
Secondary
Peak Plasma Concentration of Idelalisib
Time frame: 1.5 hours postdose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 16 | 2634.39 ng/ml | Standard Deviation 1323.611 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Day 1 | 2626.12 ng/ml | Standard Deviation 1330.29 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 20 | 2354.26 ng/ml | Standard Deviation 1440.587 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 6 | 2433.33 ng/ml | Standard Deviation 1092.969 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 24 | 2058.47 ng/ml | Standard Deviation 905.071 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 32 | 2009.71 ng/ml | Standard Deviation 1231.296 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 48 | 2655.13 ng/ml | Standard Deviation 1348.957 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 2 | 2306.12 ng/ml | Standard Deviation 810.433 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 8 | 2207.59 ng/ml | Standard Deviation 980.606 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 10 | 2435.00 ng/ml | Standard Deviation 1027.469 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 12 | 2328.13 ng/ml | Standard Deviation 1141.764 |
| Idelalisib 150 mg BID | Peak Plasma Concentration of Idelalisib | Week 4 | 2353.95 ng/ml | Standard Deviation 930.754 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 4 | 1528.48 ng/ml | Standard Deviation 759.936 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 12 | 1658.89 ng/ml | Standard Deviation 837.159 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 8 | 1649.25 ng/ml | Standard Deviation 940.683 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 20 | 1925.29 ng/ml | Standard Deviation 776.516 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 2 | 1520.29 ng/ml | Standard Deviation 675.089 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 16 | 1756.37 ng/ml | Standard Deviation 826.784 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 24 | 1914.65 ng/ml | Standard Deviation 1151.998 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 6 | 1682.52 ng/ml | Standard Deviation 939.455 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 10 | 1601.11 ng/ml | Standard Deviation 804.605 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 32 | 2028.00 ng/ml | Standard Deviation 593.236 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Day 1 | 1575.81 ng/ml | Standard Deviation 803.317 |
| Idelalisib 100 mg BID | Peak Plasma Concentration of Idelalisib | Week 48 | 1448.33 ng/ml | Standard Deviation 650.798 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 48 | 1312.00 ng/ml | Standard Deviation 850.894 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Day 1 | 2221.35 ng/ml | Standard Deviation 1621.291 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 2 | 2186.89 ng/ml | Standard Deviation 1265.85 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 4 | 2608.12 ng/ml | Standard Deviation 1009.937 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 6 | 2341.33 ng/ml | Standard Deviation 948.133 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 8 | 2786.43 ng/ml | Standard Deviation 1591.408 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 10 | 2380.00 ng/ml | Standard Deviation 1118.679 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 12 | 2316.20 ng/ml | Standard Deviation 1391.815 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 32 | 1825.00 ng/ml | Standard Deviation 947.892 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 16 | 2372.50 ng/ml | Standard Deviation 1335.42 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 20 | 2177.69 ng/ml | Standard Deviation 1417.505 |
| Idelalisib 150 mg BID INT | Peak Plasma Concentration of Idelalisib | Week 24 | 1906.30 ng/ml | Standard Deviation 1099.458 |
Secondary
Progression-Free Survival (PFS)
PFS is defined as the interval (in months) from randomization to the earlier of the first documentation of PD by IRC or death from any cause. PD criteria: New node of \>1.5 cm or \>1.0 cm to ≤1.5 cm in LD, \>1.0 cm in LPD, new/unequivocal reappearance of resolved extra-nodal lesion, new non-index disease, increase by 50% in SPD of index lesions, LD of individual node/extra-nodal mass.
Time frame: Randomization up to PD or death from any cause (maximum duration: 73.5 months)
Population: Participants in the ITT analysis set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Idelalisib 150 mg BID | Progression-Free Survival (PFS) | 9.8 months |
| Idelalisib 100 mg BID | Progression-Free Survival (PFS) | 19.4 months |
| Idelalisib 150 mg BID INT | Progression-Free Survival (PFS) | 8.3 months |
Secondary
Time to Onset of Adverse Events of Interest (AEIs)
Time to onset of AEIs is defined as the interval (in months) from the start of idelalisib treatment to the first documentation of start of AEI. AEIs included grade ≥ 3 diarrhea/colitis, rash, febrile neutropenia, infection, and any grade of: Pneumonitis, bowel perforation, progressive multifocal leukoencephalopathy (PML), Pneumocystis jirovecii pneumonia (PJP), cytomegalovirus (CMV) infection, and organizing pneumonia.
Time frame: First dose date up to 30 days after last dose of study drug (maximum 64.6 months)
Population: AEIs data was not collected for analysis.
Secondary
Trough Plasma Concentration of Idelalisib
Time frame: Predose on Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, and 48
Population: Pharmacokinetic (PK) analysis set included participants who received at least 1 dose of study drug and had at least 1 sample with detectable drug concentration. Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Day 1 | NA nanograms per milliliter (ng/ml) | — |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 2 | 683.68 nanograms per milliliter (ng/ml) | Standard Deviation 514.166 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 4 | 623.64 nanograms per milliliter (ng/ml) | Standard Deviation 466.557 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 6 | 581.20 nanograms per milliliter (ng/ml) | Standard Deviation 470.988 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 8 | 655.16 nanograms per milliliter (ng/ml) | Standard Deviation 498.873 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 10 | 616.05 nanograms per milliliter (ng/ml) | Standard Deviation 370.862 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 12 | 630.56 nanograms per milliliter (ng/ml) | Standard Deviation 664.066 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 16 | 729.23 nanograms per milliliter (ng/ml) | Standard Deviation 832.158 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 20 | 525.91 nanograms per milliliter (ng/ml) | Standard Deviation 411.33 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 24 | 460.74 nanograms per milliliter (ng/ml) | Standard Deviation 321.766 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 32 | 446.13 nanograms per milliliter (ng/ml) | Standard Deviation 450.821 |
| Idelalisib 150 mg BID | Trough Plasma Concentration of Idelalisib | Week 48 | 706.13 nanograms per milliliter (ng/ml) | Standard Deviation 580.022 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 48 | 552.13 nanograms per milliliter (ng/ml) | Standard Deviation 571.081 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Day 1 | NA nanograms per milliliter (ng/ml) | — |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 12 | 389.21 nanograms per milliliter (ng/ml) | Standard Deviation 466.104 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 20 | 745.58 nanograms per milliliter (ng/ml) | Standard Deviation 841.105 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 2 | 382.94 nanograms per milliliter (ng/ml) | Standard Deviation 352.842 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 10 | 356.12 nanograms per milliliter (ng/ml) | Standard Deviation 372.557 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 32 | 388.58 nanograms per milliliter (ng/ml) | Standard Deviation 351.293 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 4 | 447.78 nanograms per milliliter (ng/ml) | Standard Deviation 356.971 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 16 | 730.29 nanograms per milliliter (ng/ml) | Standard Deviation 936.798 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 8 | 430.33 nanograms per milliliter (ng/ml) | Standard Deviation 477.877 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 6 | 361.90 nanograms per milliliter (ng/ml) | Standard Deviation 248.996 |
| Idelalisib 100 mg BID | Trough Plasma Concentration of Idelalisib | Week 24 | 728.76 nanograms per milliliter (ng/ml) | Standard Deviation 760.391 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 6 | 596.80 nanograms per milliliter (ng/ml) | Standard Deviation 401.619 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 8 | 77.66 nanograms per milliliter (ng/ml) | Standard Deviation 274.313 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 24 | NA nanograms per milliliter (ng/ml) | — |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 10 | 387.40 nanograms per milliliter (ng/ml) | Standard Deviation 314.249 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 12 | 272.44 nanograms per milliliter (ng/ml) | Standard Deviation 626.451 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 16 | 111.67 nanograms per milliliter (ng/ml) | Standard Deviation 296.666 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 32 | 352.73 nanograms per milliliter (ng/ml) | Standard Deviation 875.923 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Day 1 | NA nanograms per milliliter (ng/ml) | — |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 2 | 636.35 nanograms per milliliter (ng/ml) | Standard Deviation 461.042 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 20 | 107.34 nanograms per milliliter (ng/ml) | Standard Deviation 269.434 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 4 | 94.14 nanograms per milliliter (ng/ml) | Standard Deviation 231.647 |
| Idelalisib 150 mg BID INT | Trough Plasma Concentration of Idelalisib | Week 48 | 165.00 nanograms per milliliter (ng/ml) | Standard Deviation 368.951 |