Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the addition of idelalisib to bendamustine/rituximab on progression-free survival (PFS) in adults with previously treated indolent non-Hodgkin lymphoma (iNHL). An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line 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 this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Conditions
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Indolent Non-Hodgkin's Lymphomas

Intervention / Treatment
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* Drug: Idelalisib
* Drug: Rituximab
* Drug: Bendamustine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following Follicular lymphoma (FL) Grade 1, 2, or 3a Small lymphocytic lymphoma (SLL) Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM) Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal) Key Exclusion Criteria: History of lymphoid malignancy other than those allowed per inclusion criteria. Ongoing drug-induced liver injury, active hepatitis C, active hepatitis B, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension. Prior treatment with bendamustine that was not effective. 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab + Bendamustine + Idelalisib<br>Participants will receive rituximab + bendamustine + idelalisib. | Drug: Idelalisib<br>* 150 mg tablet administered orally twice daily<br>* Other names: GS-1101;Drug: Rituximab<br>* 375 mg/m^2 single-use vials administered intravenously every 4 weeks (up to a total of 6 infusions)<br>* Other names: MabThera®;Drug: Bendamustine<br>* 90 mg/m^2 single-use vials administered intravenously for two consecutive days every 4 weeks (up to a total of 4-6 cycles as tolerated)<br>* Other names: Treanda®;|
| Experimental: Rituximab + Bendamustine + Placebo<br>Participants will receive rituximab + bendamustine + placebo. | Drug: Rituximab<br>* 375 mg/m^2 single-use vials administered intravenously every 4 weeks (up to a total of 6 infusions)<br>* Other names: MabThera®;Drug: Bendamustine<br>* 90 mg/m^2 single-use vials administered intravenously for two consecutive days every 4 weeks (up to a total of 4-6 cycles as tolerated)<br>* Other names: Treanda®;Drug: Placebo<br>* Tablet administered orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the interval from randomization to the earlier of the first documentation of definitive indolent non-Hodgkin lymphomas (iNHL) disease progression or death from any cause. Definitive iNHL disease progression is progression based on standard criteria. PFS was to be assessed by an independent review committee (IRC). |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate (CR) | Complete response rate is defined as the proportion of participants who achieve a complete response. CR rate was to be assessed by an IRC. |  | 
| Overall Response Rate (ORR) | Overall response rate is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response (VGPR) or minor response (MR) for participants with Waldenstrom's). ORR was to be assessed by an IRC. |  | 
| Lymph Node Response Rate | Lymph node response rate is defined as the proportion of participants who achieve ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Lymph node response rate was to be assessed by an IRC. |  | 
| Overall Survival (OS) | Overall survival is defined as the interval from randomization to death from any cause. |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iNHL, indolent NHL, follicular lymphoma, CAL-101, rituximab, bendamustine, small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, Waldenstrom macroglobulinemia, LPL, WM, Marginal zone lymphoma, MZL, SLL, FL, GS-1101, PI3K inhibitor, idelalisib