Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Indolent Non-Hodgkin's Lymphomas Clinical Trial

— Bridalveil  

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01732926
• Other study ID #: GS-US-313-0125
• Secondary ID: 2012-004034-42
• Status: Terminated
• Phase: Phase 3
• Start date: January 2, 2013
• Est. completion date: May 17, 2016

Study information

• Verified date: March 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 addition of idelalisib to bendamustine/rituximab on progression-free survival (PFS) in adults with previously treated indolent non-Hodgkin lymphoma (iNHL).

An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line 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: 475
• Est. completion date: May 17, 2016
• Est. primary completion date: May 17, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following

1. Follicular lymphoma (FL) Grade 1, 2, or 3a

2. Small lymphocytic lymphoma (SLL)

3. Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)

4. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)

Key Exclusion Criteria:

• History of lymphoid malignancy other than those allowed per inclusion criteria.

• Ongoing drug-induced liver injury, active hepatitis C, active hepatitis B, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.

• Prior treatment with bendamustine that was not effective.

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

Related Conditions & MeSH terms

• Indolent Non-Hodgkin's Lymphomas
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Idelalisib
150 mg tablet administered orally twice daily
• Rituximab
375 mg/m^2 single-use vials administered intravenously every 4 weeks (up to a total of 6 infusions)
• Bendamustine
90 mg/m^2 single-use vials administered intravenously for two consecutive days every 4 weeks (up to a total of 4-6 cycles as tolerated)
• Placebo
Tablet administered orally twice daily

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Saint Vincent's Hospital	Fitzroy	Victoria
Australia	Western Hospital	Footscray	Victoria
Australia	Adelaide Cancer Centre	Kurralta Park	South Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Haematology and Oncology Clinics of Australia Gold Coast	South Brisbane	Queensland
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hôpital Charles Lemoyne	Greenfield Park	Quebec
Canada	Queen Elizabeth II Health Sciences Centre, Centre for Clinical Research	Halifax	Nova Scotia
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Fraser Clinical Trials, Inc.	New Westminster	British Columbia
Canada	Centre Hospitalier Affilie Universitaire de Quebec	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BC Cancer Agency - Vancouver Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg
Czechia	Fakultní nemocnice Brno	Brno
Czechia	Fakultní nemocnice Hradec Králové	Hradec Králové
Czechia	Fakultní Nemocnice Ostrava	Ostrava - Poruba	Severomoravsky KRAJ
France	Institut Bergonié	Bordeaux Cedex	Aquitaine
France	Centre Hospitalier Universitaire Brest	Brest Cedex
France	Centre Hospitalier de Dunkerque	Dunkerque
France	Centre Hospitalier Départmental La Roche sur Yon	La Roche sur Yon
France	Centre Jean Bernard	Le Mans	PAYS DE LA Loire
France	Centre Léon Bérard	Lyon Cedex 08
France	Institut Paoli Calmettes	Marseille
France	CHR Metz	Metz Cedex 03	Alsace
France	Hôpital Hôtel-Dieu	Nantes cedex 1
France	Hôpital Necker-Enfants Malades	Paris	Ile-de-france
France	Centre Hospitalier Lyon Sud	Pierre Bénite Cedex	Rhone-alpes
France	Centre Hospitalier Universitaire de Poitiers	Poitiers Cedex
France	Centre Henri-Becquerel	Rouen Cedex 1	Haute-normandie
France	Centre Hospitalier Universitaire de Strasbourg - Hôpital Hautepierre	Strasbourg Cedex	Alsace
France	Centre Hospitalier Régional et Universitaire - Hôpital Bretonneau	Tours
France	Institut Gustave Roussy	Villejuif
Germany	Charite - Campus Virchow	Berlin
Germany	Vivantes Klinikum am Urban	Berlin
Germany	Gemeinschaftspraxis Dres. Söling Und Siehl	Kassel	Hessen
Germany	Klinikum der Ludwig-Maximilians-Universität München	München
Germany	Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH	Villingen-Schwenningen	Baden-wuerttemberg
Israel	Barzilai Medical Center	Ashkelon
Israel	Soroka University Medical Center	Beer Sheva
Israel	Rambam Health Corp.	Haifa
Israel	Hadassah Medical Organization, Ein Kerem	Jerusalem
Italy	Centro di Riferimento Oncologico di Aviano	Aviano
Italy	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Bologna
Italy	Spedali Civili Di Brescia Azienda Ospedaliera	Brescia
Italy	IRCCS Azienda Ospedaliera Universitaria San Martino	Genova
Italy	Azienda Ospedaliera Ospedale Niguarda Ca' Granda	Milano
Italy	Ospedale San Raffaele-IRCCS	Milano
Italy	Azienda Ospedaliero Universitaria (AOU) "Maggiore della Carita" di Novara	Novara
Italy	Azienda Ospedaliera Ospedali Riuniti Marche Nord	Pesaro
Italy	Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto	Piacenza
Italy	Azienda Ospedaliera Universitaria Senese - Policlinico S. Maria alle Scotte	Siena
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
Korea, Republic of	Dong-A University Medical Center	Busan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Malopolskie Centrum Medyczne S.C.	Kraków
Poland	Wojewódzki Szpital Specjalistyczny im. Mikolaja Kopernika w Lodzi	Lódz
Poland	Szpital Kliniczny nr 1, Katedra i Klinika Hematoonkologii i Transplantacji Szpiku	Lublin
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim	Olsztyn
Poland	Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku	Slupsk
Poland	Centralny Szpital Kliniczny MSW w Warszawie	Warszawa
Poland	Centrum Onkologii i Hipertermii	Warszawa
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Russian Federation	Central City Hospital # 7	Ekaterinburg
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	N. N. Blokhin Russian Cancer Research Center	Moscow
Russian Federation	Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko	Nizhniy Novgorod
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
Russian Federation	FGU Russian Scientific Research Institute of Hematology and Transfusiology	Saint Petersburg
Russian Federation	FSI "V.A. Almazov Federal Centre of Heart, Blood and Endocrinology of Rosmedtechnologies"	Saint Petersburg
Russian Federation	Saint Petersburg I.P. Pavlov State Medical University	Saint-Petersburg
Russian Federation	Saratov State Medical University	Saratov
Russian Federation	State Budgetary Healthcare Institution "Volgograd Regional Clinical Oncology Dispensary #1"	Volgograd
Spain	Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario de Canarias	San Cristobal de La Laguna
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari i Politecnic La Fé de Valencia	Valencia
Sweden	Karolinska Universitetssjukhuset	Huddinge	Stockholm
Sweden	Länssjukhuset Ryhov	Jönköping
Taiwan	Changhua Christian Hospital	Changhua city
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng-Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	University Hospital Coventry	Coventry	England
United Kingdom	Royal Bournemouth General Hospital	Dorset	England
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	England
United Kingdom	Barts and The London NHS Trust	London	England
United Kingdom	Guys and Saint Thomas NHS Foundation Trust	London	England
United Kingdom	Imperial College Healthcare NHS Trust	London	England
United Kingdom	University College London Hospitals National Health Society Foundation Trust	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester	England
United Kingdom	Mount Vernon Hospital	Middlesex
United Kingdom	Oxford University Hospitals NHS Trust	Oxford	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	New Cross Hospital	Wolverhampton
United States	Comprehensive Blood and Cancer Center (Bakersfield)	Bakersfield	California
United States	Texas Oncology, P.A.	Bedford	Texas
United States	Ironwood Cancer and Research Center	Chandler	Arizona
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Charles A. Sammons Cancer Center	Dallas	Texas
United States	Sylvester Comprehensive Cancer Center/UMHC	Deerfield Beach	Florida
United States	Texas Oncology, P.A.	Denton	Texas
United States	North Shore Hematology/Oncology Associates	East Setauket	New York
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Saint Jude Heritage Healthcare (TORI)	Fullerton	California
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Bon Secours Saint Francis Hospital	Greenville	South Carolina
United States	Texas Oncology, P.A.	Harlingen	Texas
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Joliet Oncology Hematology Associates Ltd.	Joliet	Illinois
United States	Pacific Shores Medical Group	Long Beach	California
United States	Northwest Georgia Oncology Centers, PC	Marietta	Georgia
United States	Signal Point Clinical Research Center, LLC	Middletown	Ohio
United States	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Weill Cornell Medical College	New York	New York
United States	Cancer Care Associates	Redondo Beach	California
United States	San Luis Obispo Oncology and Hematology	San Luis Obispo	California
United States	Cancer Center of Santa Barbara	Santa Barbara	California
United States	Central Coast Medical Oncology Group	Santa Maria	California
United States	St Joseph Heritage Healthcare System	Santa Rosa	California
United States	Swedish Medical Center	Seattle	Washington
United States	Northwest Medical Specialists	Tacoma	Washington
United States	Kaiser Permanente Vallejo Medical Center	Vallejo	California
United States	Texas Oncology, P.A.	Weslaco	Texas
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	PFS is defined as the interval from randomization to the earlier of the first documentation of definitive indolent non-Hodgkin lymphomas (iNHL) disease progression or death from any cause. Definitive iNHL disease progression is progression based on standard criteria. PFS was to be assessed by an independent review committee (IRC).
Secondary	Complete Response Rate (CR)	Complete response rate is defined as the proportion of participants who achieve a complete response. CR rate was to be assessed by an IRC.
Secondary	Overall Response Rate (ORR)	Overall response rate is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response (VGPR) or minor response (MR) for participants with Waldenstrom's). ORR was to be assessed by an IRC.
Secondary	Lymph Node Response Rate	Lymph node response rate is defined as the proportion of participants who achieve = 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Lymph node response rate was to be assessed by an IRC.
Secondary	Overall Survival (OS)	Overall survival is defined as the interval from randomization to death from any cause.