Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Adults With Previously Untreated Chronic Lymphocytic Leukemia
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
2 other identifiers
interventional
311
13 countries
91
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2014
91 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 5, 2013
CompletedFirst Posted
Study publicly available on registry
November 11, 2013
CompletedStudy Start
First participant enrolled
February 5, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 30, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 16, 2016
CompletedResults Posted
Study results publicly available
October 11, 2017
CompletedNovember 19, 2018
September 1, 2017
2.3 years
November 5, 2013
March 30, 2017
October 19, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival
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).
Up to 22 months
Secondary Outcomes (5)
Overall Response Rate
Up to 22 months
Nodal Response Rate
Up to 22 months
Complete Response Rate
Up to 22 months
Overall Survival
Up to 22 months
Minimal Residual Disease Negativity Rate at Week 36
Up to 22 months
Study Arms (2)
Idelalisib+bendamustine+rituximab
EXPERIMENTALParticipants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Placebo+bendamustine+rituximab
PLACEBO COMPARATORParticipants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Interventions
150 mg tablet administered orally twice daily
Administered intravenously at a starting dose of 90 mg/m\^2 for up to 6 cycles. Dosing will be based on mg/m\^2 of body surface area.
Single-use vials administered intravenously weekly starting at 375 mg/m\^2 on Day 1 (Week 0) and 500 mg/m\^2 thereafter for a total of 6 infusions
Placebo to match idelalisib administered orally twice daily
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (91)
St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center
Fullerton, California, 92835, United States
UCSD Moores Cancer Center
La Jolla, California, 92093, United States
Central Coast Medical Oncology
Santa Maria, California, 93454, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
Memorial Healthcare System
Hollywood, Florida, 33021, United States
Cancer Specialists of North Florida
Jacksonville, Florida, 32256, United States
Florida Cancer Specialists-South
Sarasota, Florida, 34236, United States
Franciscan Physician Network Oncology & Hematology
Indianapolis, Indiana, 46237, United States
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101, United States
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89074, United States
Hematology /Oncology Associates of Northern New Jersey
Morristown, New Jersey, 07962, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of Rochester
Rochester, New York, 14642, United States
Gabrail Cancer Center Research
Canton, Ohio, 44718, United States
Sarah Cannon Research Institute
Cincinnati, Ohio, 45242, United States
Signal Point Clinical Research Center
Middletown, Ohio, 45042, United States
Saint Francis Hospital
Greenville, South Carolina, 29601, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Texas Oncology-Austin Midtown
Austin, Texas, 78705, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84103, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
St Vincent's Hospital, Sydney
Darlinghurst, New South Wales, 2010, Australia
Jarrett Street Specialist Centre
North Gosford, New South Wales, 2250, Australia
Calvary Mater Newcastle
Waratah, New South Wales, 2298, Australia
Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Flinders Medical Centre, Department of Haematology, Level 6
Bedford Park, South Australia, 5042, Australia
Ashford Cancer Centre Research
Kurralta Park, South Australia, 5037, Australia
Queen Elizabeth Hospital
Woodville South, South Australia, 5011, Australia
Frankston Hospital
Frankston, Victoria, 3199, Australia
Barwon Health, University Hospital Geelong
Geelong, Victoria, 3220, Australia
Z N A Stuivenberg
Antwerp, 2060, Belgium
AZ Sint-Jan AV Brugge-Oostende
Bruges, 8000, Belgium
University Hospital Leuven
Leuven, 3000, Belgium
Cancercare Manitoba - Maccharles Unit
Winnipeg, Manitoba, R3E 0V9, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C9, Canada
Hôpital du Sacré-Coeur de Montréal
Montreal, Quebec, H4J 1C5, Canada
CHU de Québec - Hôpital de l'Enfant-Jésus
Québec, Quebec, G1J 1Z4, Canada
Klinicka bolnica Dubrava
Zagreb, 10000, Croatia
Klinicka bolnica Merkur
Zagreb, 10000, Croatia
UHC Zagreb
Zagreb, 10000, Croatia
Faculty hospital Ostrava
Ostrava-Poruba, Moravian-Silesian, 70852, Czechia
University Hospital
Brno, 62500, Czechia
Faculty Hospital Hradec Kralove
Hradec Králové, 500 05, Czechia
Faculty Hospital Plzen
Pilsen, 304 60, Czechia
Faculty Hospital Kralovske Vinohrady
Prague, 10034, Czechia
CHRU de Lille, Hopital Claude Huriez
Lille, 59037, France
Hospital Saint-Louis
Paris, 75010, France
CHU Bretonneau
Tours, 37044, France
Szent Borbála Hospital
Tatabánya, Komárom-Esztergom, 2800, Hungary
Kaposi Mor Oktato Korhaz, Intezeti Gyogyszertar,
Kaposvár, Somogy County, 7400, Hungary
Semmelweis University
Budapest, 1083, Hungary
National Institute of Oncology
Budapest, 1122, Hungary
University of Debrecen HSC Institute of internal Medicine, Department of Hematology
Debrecen, 4032, Hungary
Pandy Kalman Hospital
Gyula, 5700, Hungary
University Of Pecs, Medical School
Pécs, 7624, Hungary
Szegedi Tudomanyegyetem AOK - Szent-Gyorgyi Albert Klinikai Kozpont, II. Belgyógyászati Klinika
Szeged, 6725, Hungary
IRCCS Istituto Tumori
Bari, Apulia, 70024, Italy
Ospedale Oncologico Armando Businco
Cagliari, 09121, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Azienda Ospedaliero Universitaria Policlinico di Modena
Modena, 41124, Italy
AOU Maggiore della Carità
Novara, 28100, Italy
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80-952, Poland
Malopolskie Centrum Medyczne s.c.
Krakow, 30-510, Poland
Wojewodzki Szpital Specjalistyczny im. M. Kopernika Klinika Hematologii
Lodz, 93-510, Poland
Centralny Szpital Kliniczny MSW w Warszawie Klinika Onkologii i Hematologii
Warsaw, 02-507, Poland
Centrum Onkologii-Instytut Marii Sklodowskiej -Curie klinika Nowotworow Ukladu Chlonnego
Warsaw, 02-781, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu Klinika i Katedra Hematologii,Nowotworow Krwi i Transplantacji Szpiku
Wroclaw, 50-367, Poland
Dolnoslakie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
Wroclaw, 53-439, Poland
Emergency County Clinical Hospital Brasov
Brasov, 500326, Romania
Spitalul Clinic Colentina
Bucharest, 20125, Romania
Hospital Vall de Hebron
Barcelona, Catalonia, 08035, Spain
Hospital Clinic
Barcelona, Catalonia, 08036, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 8041, Spain
ICO, Hospitalet de Llobregat
Barcelona, 8908, Spain
Hospital Universitario La Princesa
Madrid, 28006, Spain
Hospital Gregorio Marañon
Madrid, 28007, Spain
Hospital Universitario Ramón Y Cajal
Madrid, 28033, Spain
Hospital 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario Puerta De Hierro
Madrid, 28222, Spain
University College London
London, England, WC1E 6BT, United Kingdom
East Kent Hospitals University NHS Foundation Trust
Canterbury, Kent, CT1 3NG, United Kingdom
Royal Marsden NHS Trust
Sutton, Surrey, SM2 5PT, United Kingdom
University Hospital of Wales
Cardiff, CF14 4XW, United Kingdom
Royal Liverpool & Broadgreen Univ. Hospitals NHS Trust
Liverpool, L7 8XP, United Kingdom
Hammersmith Hospitals NHS Trust
London, W12 0HS, United Kingdom
Oxford University Hospitals
Oxford, OX37LE, United Kingdom
University Hospital Southampton NHS Trust
Southampton, SO16 6YD, United Kingdom
Royal Wolverhampton Hospital NHS Trust, New Cross Hospital
Wolverhampton, WV10 0QP, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study was terminated in agreement with the FDA due to urgent safety measures. Due to early study termination, the prespecified efficacy analyses were not conducted. The PFS data presented are investigator assessments rather than IRC assessments.
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 5, 2013
First Posted
November 11, 2013
Study Start
February 5, 2014
Primary Completion
May 30, 2016
Study Completion
June 16, 2016
Last Updated
November 19, 2018
Results First Posted
October 11, 2017
Record last verified: 2017-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 18 months after study completion
- Access Criteria
- A secured external environment with username, password, and RSA code.
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.