Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Adults With Previously Untreated Chronic Lymphocytic Leukemia

Phase 3

Terminated

Interventions: Drug: Idelalisib
Drug: Rituximab
Drug: Bendamustine
Drug: Placebo

Brief Summary: The primary objective of this study is to evaluate the progression-free survival in participants with previously untreated chronic lymphocytic leukemia (CLL) who would otherwise be suitable for bendamustine and rituximab treatment as standard of care.

An increased rate of deaths and serious adverse events (SAEs) among participants with front-line 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 this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).

Recruitment & Eligibility

Inclusion Criteria

Documented diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
No prior therapy for CLL other than corticosteroids for disease complications
CLL that warrants treatment
Presence of measurable lymphadenopathy
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

Key

Exclusion Criteria

Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
Known presence of myelodysplastic syndrome
Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization
Ongoing liver injury
History of non-infectious pneumonitis
Ongoing inflammatory bowel disease
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
Ongoing immunosuppressive therapy other than corticosteroids
Received last dose of study drug on another therapeutic clinical trial within 30 days prior to randomization

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Arm && Interventions

Group	Intervention	Description
Placebo+bendamustine+rituximab	Rituximab	Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Idelalisib+bendamustine+rituximab	Bendamustine	Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Placebo+bendamustine+rituximab	Placebo	Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Idelalisib+bendamustine+rituximab	Idelalisib	Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Placebo+bendamustine+rituximab	Bendamustine	Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Idelalisib+bendamustine+rituximab	Rituximab	Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	Up to 22 months	Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone. PFS was to be assessed by an independent review committee (IRC).

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	Up to 22 months	Overall response rate (ORR) is defined as the proportion of participants who achieve a confirmed complete or partial response. ORR was to be assessed by an IRC.
Minimal Residual Disease Negativity Rate at Week 36	Up to 22 months	Minimal residual disease (MRD) negativity rate is defined as the proportion of participants with MRD \< 10\^-4 assessed by flow cytometry in bone marrow at Week 36 after therapy initiation or at least 12 weeks after the last dose of rituximab or bendamustine (whichever is later) for participants receiving the final dose of rituximab after the original scheduled date. MRD negativity rate was to be assessed by an IRC.
Overall Survival	Up to 22 months	Overall survival is defined as the interval from randomization to death from any cause. Overall survival was to be assessed by an IRC.
Nodal Response Rate	Up to 22 months	Nodal response rate is defined as the proportion of participants who achieve a 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Nodal response rate was to be assessed by an IRC.
Complete Response Rate	Up to 22 months	Complete response rate is defined as the proportion of participants who achieve a confirmed complete response. Complete response rate was to be assessed by an IRC.

Locations (90): St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center
🇺🇸
Fullerton, California, United States
UCSD Moores Cancer Center
🇺🇸
La Jolla, California, United States
Central Coast Medical Oncology
🇺🇸
Santa Maria, California, United States
Georgetown University
🇺🇸
Washington, District of Columbia, United States
Memorial Healthcare System
🇺🇸
Hollywood, Florida, United States
Cancer Specialists of North Florida
🇺🇸
Jacksonville, Florida, United States
Florida Cancer Specialists-South
🇺🇸
Sarasota, Florida, United States
Franciscan Physician Network Oncology & Hematology
🇺🇸
Indianapolis, Indiana, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸
Sioux City, Iowa, United States
Center for Cancer and Blood Disorders
🇺🇸
Bethesda, Maryland, United States
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St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center
🇺🇸Fullerton, California, United States