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

Indolent Non-Hodgkin's Lymphomas Clinical Trial

— Yosemite  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01732913
• Other study ID #: GS-US-313-0124
• Status: Terminated
• Phase: Phase 3
• Start date: January 16, 2013
• Est. completion date: May 18, 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 effect of the addition of idelalisib to 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: 295
• Est. completion date: May 18, 2016
• Est. primary completion date: May 18, 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) with absolute lymphocyte count < 5 x 10^9/L at the time of diagnosis

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.

• Received previous treatment with rituximab 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:
• Placebo
Tablets administered orally twice daily
• Rituximab
375 mg/m^2 administered intravenously weekly for 4 weeks, then every 8 weeks (up to a total of 8 infusions)
• Idelalisib
150 mg tablets administered orally twice daily

Locations

Country	Name	City	State
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
Australia	Haematology and Oncology Clinics of Australia at Chermside	Milton	Queensland
Australia	Fiona Stanley Hospital	Murdoch
Australia	Royal Perth Hospital	Perth	Western Australia
Czechia	Fakultní nemocnice Hradec Králové	Hradec Králové
France	Centre Hospitalier Universitaire Brest	Brest
France	Centre Hospitalier de Dunkerque	Dunkerque
France	Centre Hospitalier de Versailles	Le Chesnay
France	Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez	Lille cedex	NORD Pas-de-calais
France	Centre Léon Bérard	Lyon Cedex 08
France	Hôpital Hôtel-Dieu	Nantes cedex 1
France	Hôpital Necker-Enfants Malades	Paris	Ile-de-france
France	University Hospital of Bordeaux	Pessac	Aquitaine
France	Centre Hospitalier Lyon Sud	Pierre Bénite Cedex
France	Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie	Poitiers Cedex
Germany	Gemeinschaftspraxis Dres. Söling Und Siehl	Kassel	Hessen
Germany	Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH	Villingen-Schwenningen	Baden-wuerttemberg
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Orvos-és Egészségtudományi Centrum	Debrecen	Hajdu-bihar
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár	Somogy
Hungary	Markusovszky Egyetemi Oktatókórház	Szombathely	VAS
Israel	Hadassah Medical Organization, Ein Kerem	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Italy	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliero Universitaria (AOU) "Maggiore della Carita" di Novara	Novara
Italy	Azienda Ospedaliera Ospedali Riuniti Marche Nord	Pesaro
Italy	Centro di Riferimento Oncologico di Aviano	Pordenone
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Hospital Organization Kumamoto Medical Center	Chuo-ku	Kumamoto
Japan	Tokai University Hospital	Isehara-shi	Kanagawa
Japan	Kobe City Medical Center General Hospital	Kobe-city	Hyogo
Japan	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Minami Ku	Fukuoka
Japan	Toranomon Hospital	Minato-ku	Tokyo
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Nagoya City University Hospital	Nagoya City	Aichi
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi	Aichi
Japan	Okayama University Hospital	Okayama-city	Okayama
Japan	Osaka City University Hospital	Osaka-shi	Osaka
Japan	Tohoku University Hospital	Sendai	Miyagi
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Malopolskie Centrum Medyczne S.C.	Kraków
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim	Olsztyn
Poland	Centrum Onkologii i Hipertermii	Warszawa
Portugal	Hospital Geral de Santo António do Centro Hospitalar do Porto	Porto
Romania	Institutul Clinic Fundeni	Bucuresti
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko	Nizhniy Novgorod
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
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
Singapore	Gleneagles Medical Centre	Singapore
Singapore	National Cancer Centre Singapore	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
Sweden	Skånes Universitetssjukhus, Malmö	Malmö
Taiwan	Chang Gung Memorial Hospital (CGMH)	Kaohsiung
Taiwan	Tri-Service General Hospital	Taipei
United Kingdom	Barts and The London NHS Trust	London	England
United Kingdom	Mount Vernon Hospital	Middlesex
United Kingdom	Sunderland Royal Infirmary	Sunderland
United States	Texas Oncology, P.A.	Bedford	Texas
United States	Montefiore Medical Center	Bronx	New York
United States	Ironwood Cancer and Research Center	Chandler	Arizona
United States	Tennessee Oncology, PLLC	Chattanooga	Tennessee
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Wayne State University	Detroit	Michigan
United States	City of Hope Cancer Center	Duarte	California
United States	Florida Cancer Specialists and Research Institute	Fort Myers	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Center for Cancer and Blood Disorders, PC	Fort Worth	Texas
United States	Saint Jude Heritage Healthcare	Fullerton	California
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Pacific Shores Medical Group	Long Beach	California
United States	UCLA Medical Center	Los Angeles	California
United States	Middlesex Hospital Cancer Center	Middletown	Connecticut
United States	Signal Point Clinical Research Center, LLC	Middletown	Ohio
United States	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Cancer Care Associates	Redondo Beach	California
United States	Cancer Center of Santa Barbara	Santa Barbara	California
United States	Central Coast Medical Oncology Group	Santa Maria	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Prairie Lakes Healthcare System	Watertown	South Dakota
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Shenandoah Oncology Associates, PC	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  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 earlier of the first documentation of definitive indolent non-Hodgkin lymphoma (iNHL) disease progression or death from any cause. PFS was to be assessed by an independent review committee (IRC).
Secondary	Overall Response Rate	Overall Response Rate (ORR) is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response or minor response 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	Complete Response Rate	Complete response rate is defined as the proportion of participants who achieve a complete response. Complete response rate was to be assessed by an IRC.
Secondary	Overall Survival	Overall survival is defined as the interval from randomization to death from any cause.