Idelalisib in Combination With Rituximab for Previously Untreated Follicular Lymphoma and Small Lymphocytic Lymphoma

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Single Arm Study Evaluating the Safety and Efficacy of Idelalisib in Combination With Rituximab for Previously Untreated Follicular Lymphoma and Small Lymphocytic Lymphoma

Conditions
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Follicular Lymphoma, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Idelalisib
* Biological: Rituximab


Participation Criteria
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Eligibility Criteria
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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/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idelalisib + rituximab<br>Idelalisib + rituximab for up to 104 weeks | Drug: Idelalisib<br>* 150 tablets administered orally twice daily<br>* Other names: GS-1101;Biological: Rituximab<br>* 375 mg/m^2 administered intravenously (weekly for 4 weeks and then every 8 weeks from Week 12 up to Week 100)<br>* Other names: MabThera®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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. | Up to 24 weeks plus 30 days | 
| 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. |  | 
| 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. |  | 
| 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. |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Indolent Non-Hodgkin Lymphoma, FL, SLL