A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Untreated Chronic Lymphocytic Leukemia
Overview
- Phase
- Phase 3
- Intervention
- Idelalisib
- Conditions
- Chronic Lymphocytic Leukemia
- Sponsor
- Gilead Sciences
- Enrollment
- 311
- Locations
- 90
- Primary Endpoint
- Progression-Free Survival
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
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).
Investigators
Eligibility Criteria
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
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.
Arms & Interventions
Idelalisib+bendamustine+rituximab
Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Intervention: Idelalisib
Idelalisib+bendamustine+rituximab
Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Intervention: Bendamustine
Idelalisib+bendamustine+rituximab
Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Intervention: Rituximab
Placebo+bendamustine+rituximab
Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Intervention: Bendamustine
Placebo+bendamustine+rituximab
Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Intervention: Rituximab
Placebo+bendamustine+rituximab
Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression-Free Survival
Time Frame: 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 Outcomes
- Overall Response Rate(Up to 22 months)
- Minimal Residual Disease Negativity Rate at Week 36(Up to 22 months)
- Overall Survival(Up to 22 months)
- Nodal Response Rate(Up to 22 months)
- Complete Response Rate(Up to 22 months)