Efficacy and Safety of Idelalisib (GS-1101) in Combination With 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 effect of the addition of idelalisib to 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 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: Placebo
* Drug: Rituximab
* Drug: Idelalisib


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) with absolute lymphocyte count < 5 x 10^9/L at the time of diagnosis 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. Received previous treatment with rituximab 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 + idelalisib<br>Participants will receive rituximab + idelalisib. | Drug: Rituximab<br>* 375 mg/m^2 administered intravenously weekly for 4 weeks, then every 8 weeks (up to a total of 8 infusions)<br>* Other names: MabThera®;Drug: Idelalisib<br>* 150 mg tablets administered orally twice daily<br>* Other names: Zydelig®;|
| Placebo Comparator: Rituximab + Placebo<br>Participants will receive rituximab + placebo. Following confirmation of iNHL disease progression by the independent review committee and unblinding, participants may be eligible to receive open-label idelalisib 150 mg twice daily. | Drug: Placebo<br>* Tablets administered orally twice daily<br>Drug: Rituximab<br>* 375 mg/m^2 administered intravenously weekly for 4 weeks, then every 8 weeks (up to a total of 8 infusions)<br>* Other names: MabThera®;Drug: Idelalisib<br>* 150 mg tablets administered orally twice daily<br>* Other names: Zydelig®;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall Response Rate (ORR) is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response or minor response 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. |  | 
| Complete Response Rate | Complete response rate is defined as the proportion of participants who achieve a complete response. Complete response rate was to be assessed by an IRC. |  | 
| Overall Survival | 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, Small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, Waldenstrom macroglobulinemia, LPL, WM, Marginal zone lymphoma, MZL, SLL, FL, GS-1101, idelalisib