Follicular Lymphoma, Small Lymphocytic Lymphoma
Conditions
Keywords
Cancer, Indolent Non-Hodgkin Lymphoma, FL, SLL
Brief summary
The primary objective of this study is to evaluate the overall response rate (ORR) and complete response (CR) rate to treatment with idelalisib in combination with rituximab in previously untreated adults with follicular lymphoma (FL) or small lymphocytic lymphoma (SLL). An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated those studies in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA). All front-line studies of idelalisib, including this study, were also terminated.
Interventions
DRUGIdelalisib
150 tablets administered orally twice daily
BIOLOGICALRituximab
375 mg/m\^2 administered intravenously (weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically confirmed diagnosis of B-cell lymphoma * No previous systemic treatment for lymphoma * Subject demonstrates need for treatment for lymphoma * Ann-Arbor Stage 2 (noncontiguous), 3, or 4 disease * Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy * Adequate performance status * Required baseline laboratory data within protocol-specified parameters Key
Exclusion criteria
* Known history of transformed lymphoma or diffuse large cell lymphoid malignancy * Known history of, or clinically apparent, central nervous system (CNS) lymphoma or leptomeningeal lymphoma * 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 (HBV), chronic active hepatitis C (HCV), alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, portal hypertension, primary biliary cirrhosis, or ongoing extrahepatic obstruction caused by cholelithiasis * 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 Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | — | Overall response rate (ORR) was defined as the proportion of participants who achieve a confirmed complete or partial response during idelalisib treatment. ORR was to be assessed by an independent review committee (IRC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings | Up to 24 weeks plus 30 days | The rate of Grade ≥ 3 transaminase elevations was defined as the number of participants with any Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations. |
| Idelalisib Trough and Peak Plasma Concentrations | Predose and 1.5 hour postdose at Weeks 2, 4, and 12 | — |
| Time to Response | — | Time to response was defined as the the interval from the start of idelalisib treatment to the first documentation of complete or partial response. |
| Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Up to 24 weeks plus 30 days | — |
| Progression-Free Survival | — | Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression or death from any cause. |
| Overall Survival | — | Overall survival was defined as the interval from enrollment to death from any cause. |
| Changes in Health-Related Quality of Life | — | Changes in health-related quality of life was to be reported by participants using the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) questionnaire. |
| Duration of Response | — | Duration of response (DOR) was defined as the interval from the first documentation of complete response or partial response to the earlier of the first documentation of disease progression or death from any cause. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 14 September 2015. The last study visit occurred on 03 May 2016.
Pre-assignment details
20 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Idelalisib + Rituximab Idelalisib 150 mg tablet twice daily for up to 104 weeks + rituximab 375 mg/m\^2 intravenously (once weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100) | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Study Terminated by Sponsor | 9 |
Baseline characteristics
| Characteristic | Idelalisib + Rituximab |
|---|---|
| Age, Continuous | 69 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 9 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
Overall Response Rate
Overall response rate (ORR) was defined as the proportion of participants who achieve a confirmed complete or partial response during idelalisib treatment. ORR was to be assessed by an independent review committee (IRC).
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
Changes in Health-Related Quality of Life
Changes in health-related quality of life was to be reported by participants using the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) questionnaire.
Population: Due to the early termination of the study, data were not available for all participants, and therefore this prespecified analysis was not conducted.
Secondary
Duration of Response
Duration of response (DOR) was defined as the interval from the first documentation of complete response or partial response to the earlier of the first documentation of disease progression or death from any cause.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
Idelalisib Trough and Peak Plasma Concentrations
Time frame: Predose and 1.5 hour postdose at Weeks 2, 4, and 12
Population: Pharmacokinetic (PK) Analysis Set: all 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idelalisib + Rituximab | Idelalisib Trough and Peak Plasma Concentrations | Week 2 predose | 216.2 ng/mL | Standard Deviation 161.73 |
| Idelalisib + Rituximab | Idelalisib Trough and Peak Plasma Concentrations | Week 4 1.5 hours postdose | 2084.3 ng/mL | Standard Deviation 1346.26 |
| Idelalisib + Rituximab | Idelalisib Trough and Peak Plasma Concentrations | Week 12 predose | 290.5 ng/mL | Standard Deviation 373.08 |
| Idelalisib + Rituximab | Idelalisib Trough and Peak Plasma Concentrations | Week 12 1.5 hours postdose | 1313.1 ng/mL | Standard Deviation 1474.87 |
| Idelalisib + Rituximab | Idelalisib Trough and Peak Plasma Concentrations | Week 2 1.5 hours postdose | 2240.0 ng/mL | Standard Deviation 880.03 |
| Idelalisib + Rituximab | Idelalisib Trough and Peak Plasma Concentrations | Week 4 predose | 347.4 ng/mL | Standard Deviation 365.57 |
Secondary
Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death
Time frame: Up to 24 weeks plus 30 days
Population: Intent-to-Treat (ITT) Analysis Set: all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Idelalisib + Rituximab | Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Any AE | 90.0 percentage of participants |
| Idelalisib + Rituximab | Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Any SAEs | 30.0 percentage of participants |
| Idelalisib + Rituximab | Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Any AE Leading to Idelalisib Interruption | 60.0 percentage of participants |
| Idelalisib + Rituximab | Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Any AE Leading to Idelalisib Dose Reduction | 30.0 percentage of participants |
| Idelalisib + Rituximab | Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Any AE Leading to Premature Discontinuation of IDL | 10.0 percentage of participants |
| Idelalisib + Rituximab | Overall Safety Profile of Idelalisib as Measured by the Incidence of Adverse Events (AEs), Severe AEs (SAEs), AEs Leading to Idelalisib (IDL) Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Any AE Leading to Death | 0 percentage of participants |
Secondary
Overall Survival
Overall survival was defined as the interval from enrollment to death from any cause.
Population: Due to the early termination of the study, efficacy data were not mature for all participants, and therefore the prespecified analyses were not conducted.
Secondary
Progression-Free Survival
Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression or death from any cause.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
Secondary
Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings
The rate of Grade ≥ 3 transaminase elevations was defined as the number of participants with any Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations.
Time frame: Up to 24 weeks plus 30 days
Population: ITT Analysis Set: all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Idelalisib + Rituximab | Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings | Any Grade 3 or 4 ALT Elevation | 40.0 percentage of participants |
| Idelalisib + Rituximab | Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings | Any Grade 3 or 4 AST Elevation | 10.0 percentage of participants |
Secondary
Time to Response
Time to response was defined as the the interval from the start of idelalisib treatment to the first documentation of complete or partial response.
Population: Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.