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

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

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.

Study Overview

• Status: Terminated
• Conditions: Follicular Lymphoma; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Idelalisib; Biological: Rituximab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prarie Lakes Health Care Systems, Inc.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure 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 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.

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2015
• Primary Completion (Actual): April 12, 2016
• Study Completion (Actual): May 3, 2016

Study Registration Dates

• First Submitted: October 3, 2014
• First Submitted That Met QC Criteria: October 6, 2014
• First Posted (Estimate): October 7, 2014

Study Record Updates

• Last Update Posted (Actual): May 14, 2019
• Last Update Submitted That Met QC Criteria: May 1, 2019
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; FL; SLL; Indolent Non-Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Lymphoma; Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab; Idelalisib
• Other Study ID Numbers: GS-US-313-1414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No