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

• Tumor control [ Time Frame: Every 12 weeks until progression ] [ Designated as safety issue: No ]
  To evaluate the effect of the addition of idelalisib (GS-1101) to rituximab on the onset, magnitude, and duration of tumor control
• Overall well-being [ Time Frame: The interval from randomization to death from any cause. ] [ Designated as safety issue: Yes ]
  To assess the effect of the addition of idelalisib (GS-1101) to rituximab on measures of subject well-being, including overall survival, health related quality of life, and performance status
• Safety Profile [ Time Frame: 30 days post last dose and every 12 weeks until progression. ] [ Designated as safety issue: Yes ]
  To describe the overall safety profile observed with the addition of idelalisib (GS-1101) to rituximab characterized by the type, frequency, severity, timing of onset, duration, and relationship to study therapy of any adverse events or abnormalities of laboratory tests; serious adverse events; or adverse events leading to discontinuation of study treatment

• Tumor control [ Designated as safety issue: No ]
  To evaluate the effect of the addition of GS-1101 to rituximab on the onset, magnitude, and duration of tumor control
• Overall well-being [ Designated as safety issue: Yes ]
  To assess the effect of the addition of GS-1101 to rituximab on measures of subject well-being, including overall survival, health related quality of life, and performance status
• Safety Profile [ Designated as safety issue: Yes ]
  To describe the overall safety profile observed with the addition of GS-1101 to rituximab characterized by the type, frequency, severity, timing of onset, duration, and relationship to study therapy of any adverse events or abnormalities of laboratory tests; serious adverse events; or adverse events leading to discontinuation of study treatment

The purpose of this study is to evaluate the effect of idelalisib (GS-1101) on the onset, magnitude, and duration of tumor control

This is a Phase 3, multicenter, 2-arm, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of the phosphatidylinositol 3-kinase delta (PI3K-delta) inhibitor idelalisib (GS-1101) in combination with Rituximab for previously treated indolent non-hodgkin lymphomas.

Eligible subjects will be randomized with a 2:1 allocation to Regimen A vs. Regimen B.

• Drug: idelalisib
  Other Names:

  • GS-1101
  • CAL-101
  • PI3K inhibitor
• Drug: Rituximab
• Drug: Placebo

• Experimental: Regimen A
  Rituximab IV 375 mg/m2 weekly x 4, then every 8 weeks x 4; idelalisib (GS-1101) orally 150 mg BID until disease progression
  Interventions:

  • Drug: idelalisib
  • Drug: Rituximab
• Active Comparator: Regimen B
  Rituximab IV 375 mg/m2 weekly x 4, then every 8 weeks x 4; Placebo orally 150 mg BID until disease progression
  Interventions:

  • Drug: Rituximab
  • Drug: Placebo

Inclusion Criteria:

• Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:

  1. Follicular lymphoma (FL) Grade 1, 2, or 3a
  2. Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5 x 109/L at the time of diagnosis
  3. Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
  4. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)

Exclusion Criteria:

• Known histological transformation to an aggressive lymphoma.
• 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.