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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01980888
• Other study ID #: GS-US-312-0123
• Secondary ID: 2013-003313-17
• Status: Terminated
• Phase: Phase 3
• Start date: February 5, 2014
• Est. completion date: June 16, 2016

Study information

• Verified date: September 2017
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Terminated
• Enrollment: 311
• Est. completion date: June 16, 2016
• Est. primary completion date: May 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Idelalisib
150 mg tablet administered orally twice daily
• Bendamustine
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.
• Rituximab
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
Placebo to match idelalisib administered orally twice daily

Locations

Country	Name	City	State
Australia	Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre, Department of Haematology, Level 6	Bedford Park	South Australia
Australia	St Vincent's Hospital, Sydney	Darlinghurst	New South Wales
Australia	Frankston Hospital	Frankston	Victoria
Australia	Barwon Health, University Hospital Geelong	Geelong	Victoria
Australia	Ashford Cancer Centre Research	Kurralta Park	South Australia
Australia	Jarrett Street Specialist Centre	North Gosford	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Queen Elizabeth Hospital	Woodville South	South Australia
Belgium	Z N A Stuivenberg	Antwerpen
Belgium	AZ Sint-Jan AV Brugge-Oostende	Brugge
Belgium	University Hospital Leuven	Leuven
Canada	Hôpital du Sacré-Coeur de Montréal	Montréal	Quebec
Canada	CHU de Québec - Hôpital de l'Enfant-Jésus	Quebec City	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Cancercare Manitoba - Maccharles Unit	Winnipeg	Manitoba
Croatia	Klinicka bolnica Dubrava	Zagreb
Croatia	Klinicka bolnica Merkur	Zagreb
Croatia	UHC Zagreb	Zagreb
Czechia	University Hospital	Brno
Czechia	Faculty Hospital Hradec Kralove	Hradec Kralove
Czechia	Faculty hospital Ostrava	Ostrava-Poruba	Moravian-Silesian
Czechia	Faculty Hospital Plzen	Plzen
Czechia	Faculty Hospital Kralovske Vinohrady	Prague 10
France	CHRU de Lille, Hopital Claude Huriez	Lille
France	Hospital Saint-Louis	Paris
France	CHU Bretonneau	Tours
Hungary	National Institute of Oncology	Budapest
Hungary	Semmelweis University	Budapest
Hungary	University of Debrecen HSC Institute of internal Medicine, Department of Hematology	Debrecen
Hungary	Pandy Kalman Hospital	Gyula
Hungary	Kaposi Mor Oktato Korhaz, Intezeti Gyogyszertar,	Kaposvar	Somogy
Hungary	University Of Pecs, Medical School	Pecs
Hungary	Szegedi Tudomanyegyetem AOK - Szent-Gyorgyi Albert Klinikai Kozpont, II. Belgyógyászati Klinika	Szeged
Hungary	Szent Borbála Hospital	Tatabánya	Komárom - Esztergom
Italy	IRCCS Istituto Tumori	Bari	Puglia
Italy	Ospedale Oncologico Armando Businco	Cagliari
Italy	Ospedale San Raffaele	Milan
Italy	Azienda Ospedaliero Universitaria Policlinico di Modena	Modena
Italy	AOU Maggiore della Carità	Novara
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Malopolskie Centrum Medyczne s.c.	Krakow
Poland	Wojewodzki Szpital Specjalistyczny im. M. Kopernika Klinika Hematologii	Lodz
Poland	Centralny Szpital Kliniczny MSW w Warszawie Klinika Onkologii i Hematologii	Warsaw
Poland	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
Romania	Emergency County Clinical Hospital Brasov	Brasov
Romania	Spitalul Clinic Colentina	Bucharest
Spain	Hospital Clinic	Barcelona	Cataluña
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall de Hebron	Barcelona	Cataluña
Spain	ICO, Hospitalet de Llobregat	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Gregorio Marañon	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Universitario Puerta De Hierro	Madrid
Spain	Hospital Universitario Ramón Y Cajal	Madrid
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury	Kent
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Royal Liverpool & Broadgreen Univ. Hospitals NHS Trust	Liverpool
United Kingdom	Hammersmith Hospitals NHS Trust	London
United Kingdom	University College London	London	England
United Kingdom	Oxford University Hospitals	Oxford
United Kingdom	University Hospital Southampton NHS Trust	Southampton
United Kingdom	Royal Marsden NHS Trust	Sutton	Surrey
United Kingdom	Royal Wolverhampton Hospital NHS Trust, New Cross Hospital	Wolverhampton
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Sarah Cannon Research Institute	Cincinnati	Ohio
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center	Fullerton	California
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Memorial Healthcare System	Hollywood	Florida
United States	Franciscan Physician Network Oncology & Hematology	Indianapolis	Indiana
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	Hematology /Oncology Associates of Northern New Jersey	Morristown	New Jersey
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	University of Rochester	Rochester	New York
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Central Coast Medical Oncology	Santa Maria	California
United States	Florida Cancer Specialists-South	Sarasota	Florida
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Croatia,  Czechia,  France,  Hungary,  Italy,  Poland,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Response Rate	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.	Up to 22 months
Secondary	Nodal Response Rate	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.	Up to 22 months
Secondary	Complete Response Rate	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.	Up to 22 months
Secondary	Overall Survival	Overall survival is defined as the interval from randomization to death from any cause. Overall survival was to be assessed by an IRC.	Up to 22 months
Secondary	Minimal Residual Disease Negativity Rate at Week 36	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.	Up to 22 months