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

Phase 2

Terminated

• Conditions: Small Lymphocytic Lymphoma; Follicular Lymphoma
• Interventions: Drug: Idelalisib; Biological: Rituximab

• Registration Number: NCT02258529
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-03
• Study First Submitted QC: 2014-10-06
• Study First Posted: 2014-10-07
• Study Start: 2015-09-14
• Primary Completion: 2016-04-12
• Study Completion: 2016-05-03
• Status Verified: 2017-04
• Results First Submitted: 2017-04-11
• Results First Submitted QC: 2017-04-11
• Results First Posted: 2017-05-18
• Last Update Submitted: 2019-05-01
• Last Update Posted: 2019-05-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Idelalisib + rituximab	Rituximab	Idelalisib + rituximab for up to 104 weeks
Idelalisib + rituximab	Idelalisib	Idelalisib + rituximab for up to 104 weeks

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Idelalisib Trough and Peak Plasma Concentrations	Predose and 1.5 hour postdose at Weeks 2, 4, and 12
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
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.
Overall Survival		Overall survival was defined as the interval from enrollment to death from any cause.
Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings	Up to 24 weeks plus 30 days	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.
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.

Trial Locations

Locations (6)

Pacific Shores Medical Group; 🇺🇸 Long Beach, California, United States

Prarie Lakes Health Care Systems, Inc.; 🇺🇸 Watertown, South Dakota, United States

St. Agnes Hospital; 🇺🇸 Baltimore, Maryland, United States

Florida Cancer Specialists; 🇺🇸 Fort Myers, Florida, United States

Tennessee Oncology, PLLC; 🇺🇸 Nashville, Tennessee, United States

Northwest Medical Specialties, PLLC; 🇺🇸 Tacoma, Washington, United States