Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Adults With Previously Untreated Chronic Lymphocytic Leukemia
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT01980888
- Lead Sponsor
- Gilead Sciences
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 311
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- 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.
Trial Locations
- Locations (90)
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Cancercare Manitoba - Maccharles Unit
🇨🇦Winnipeg, Manitoba, Canada
Franciscan Physician Network Oncology & Hematology
🇺🇸Indianapolis, Indiana, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Rochester
🇺🇸Rochester, New York, United States
Barwon Health, University Hospital Geelong
🇦🇺Geelong, Victoria, Australia
Klinicka bolnica Merkur
🇭🇷Zagreb, Croatia
East Kent Hospitals University NHS Foundation Trust
🇬🇧Canterbury, Kent, United Kingdom
Emergency County Clinical Hospital Brasov
🇷🇴Brasov, Romania
Georgetown University
🇺🇸Washington, District of Columbia, United States
University of Debrecen HSC Institute of internal Medicine, Department of Hematology
🇭🇺Debrecen, Hungary
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Pomorskie, Poland
Wojewodzki Szpital Specjalistyczny im. M. Kopernika Klinika Hematologii
🇵🇱Lodz, Poland
St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center
🇺🇸Fullerton, California, United States
Florida Cancer Specialists-South
🇺🇸Sarasota, Florida, United States
Central Coast Medical Oncology
🇺🇸Santa Maria, California, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Hematology /Oncology Associates of Northern New Jersey
🇺🇸Morristown, New Jersey, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Texas Oncology-Austin Midtown
🇺🇸Austin, Texas, United States
Signal Point Clinical Research Center
🇺🇸Middletown, Ohio, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
St Vincent's Hospital, Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Flinders Medical Centre, Department of Haematology, Level 6
🇦🇺Bedford Park, South Australia, Australia
Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Frankston Hospital
🇦🇺Frankston, Victoria, Australia
AZ Sint-Jan AV Brugge-Oostende
🇧🇪Brugge, Belgium
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Z N A Stuivenberg
🇧🇪Antwerpen, Belgium
University Hospital Leuven
🇧🇪Leuven, Belgium
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hôpital du Sacré-Coeur de Montréal
🇨🇦Montréal, Quebec, Canada
Klinicka bolnica Dubrava
🇭🇷Zagreb, Croatia
Faculty hospital Ostrava
🇨🇿Ostrava-Poruba, Moravian-Silesian, Czechia
CHU de Québec - Hôpital de l'Enfant-Jésus
🇨🇦Quebec City, Quebec, Canada
Szent Borbála Hospital
🇭🇺Tatabánya, Komárom - Esztergom, Hungary
UHC Zagreb
🇭🇷Zagreb, Croatia
Faculty Hospital Hradec Kralove
🇨🇿Hradec Kralove, Czechia
CHRU de Lille, Hopital Claude Huriez
🇫🇷Lille, France
University Hospital
🇨🇿Brno, Czechia
Kaposi Mor Oktato Korhaz, Intezeti Gyogyszertar,
🇭🇺Kaposvar, Somogy, Hungary
Faculty Hospital Kralovske Vinohrady
🇨🇿Prague 10, Czechia
CHU Bretonneau
🇫🇷Tours, France
Hospital Saint-Louis
🇫🇷Paris, France
Faculty Hospital Plzen
🇨🇿Plzen, Czechia
Ospedale San Raffaele
🇮🇹Milan, Italy
Semmelweis University
🇭🇺Budapest, Hungary
National Institute of Oncology
🇭🇺Budapest, Hungary
Szegedi Tudomanyegyetem AOK - Szent-Gyorgyi Albert Klinikai Kozpont, II. Belgyógyászati Klinika
🇭🇺Szeged, Hungary
Azienda Ospedaliero Universitaria Policlinico di Modena
🇮🇹Modena, Italy
University Of Pecs, Medical School
🇭🇺Pecs, Hungary
Pandy Kalman Hospital
🇭🇺Gyula, Hungary
IRCCS Istituto Tumori
🇮🇹Bari, Puglia, Italy
Ospedale Oncologico Armando Businco
🇮🇹Cagliari, Italy
Malopolskie Centrum Medyczne s.c.
🇵🇱Krakow, Poland
Centralny Szpital Kliniczny MSW w Warszawie Klinika Onkologii i Hematologii
🇵🇱Warsaw, Poland
AOU Maggiore della Carità
🇮🇹Novara, Italy
Centrum Onkologii-Instytut Marii Sklodowskiej -Curie klinika Nowotworow Ukladu Chlonnego
🇵🇱Warszawa, Poland
Dolnoslakie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
🇵🇱Wroclaw, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu Klinika i Katedra Hematologii,Nowotworow Krwi i Transplantacji Szpiku
🇵🇱Wroclaw, Poland
Hospital Vall de Hebron
🇪🇸Barcelona, Cataluña, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Clinic
🇪🇸Barcelona, Cataluña, Spain
Spitalul Clinic Colentina
🇷🇴Bucharest, Romania
ICO, Hospitalet de Llobregat
🇪🇸Barcelona, Spain
Hospital Universitario Ramón Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario La Princesa
🇪🇸Madrid, Spain
Hospital Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Puerta De Hierro
🇪🇸Madrid, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
University Hospital Southampton NHS Trust
🇬🇧Southampton, United Kingdom
Hammersmith Hospitals NHS Trust
🇬🇧London, United Kingdom
Royal Marsden NHS Trust
🇬🇧Sutton, Surrey, United Kingdom
Oxford University Hospitals
🇬🇧Oxford, United Kingdom
Royal Wolverhampton Hospital NHS Trust, New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Royal Liverpool & Broadgreen Univ. Hospitals NHS Trust
🇬🇧Liverpool, United Kingdom
Jarrett Street Specialist Centre
🇦🇺North Gosford, New South Wales, Australia
Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Ashford Cancer Centre Research
🇦🇺Kurralta Park, South Australia, Australia
University College London
🇬🇧London, England, United Kingdom
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States