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

October 19, 2018 updated by: Gilead Sciences

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

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

295

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Kurralta Park, Australia, SA 5037
        • Adelaide Cancer Centre
      • Murdoch, Australia, 6150
        • Fiona Stanley Hospital
    • Queensland
      • Milton, Queensland, Australia, 4064
        • Haematology and Oncology Clinics of Australia at Chermside
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre
      • Fitzroy, Victoria, Australia, 3065
        • Saint Vincent's Hospital
      • Footscray, Victoria, Australia, 3011
        • Western Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
  • Czechia
      • Hradec Králové, Czechia, 500 05
        • Fakultní nemocnice Hradec Králové
  • France
      • Brest, France, 29609
        • Centre Hospitalier Universitaire Brest
      • Dunkerque, France, 59385
        • Centre Hospitalier de Dunkerque
      • Le Chesnay, France, 78157
        • Centre Hospitalier de Versailles
      • Lyon Cedex 08, France, 69373
        • Centre Léon Bérard
      • Nantes cedex 1, France, 44093
        • Hôpital Hôtel-Dieu
      • Pierre Bénite Cedex, France, 69495
        • Centre Hospitalier Lyon Sud
      • Poitiers Cedex, France, 86000
        • Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie
    • Aquitaine
      • Pessac, Aquitaine, France, 33604
        • University Hospital of Bordeaux
    • Ile-de-france
      • Paris, Ile-de-france, France, 75015
        • Hôpital Necker-Enfants Malades
    • NORD Pas-de-calais
      • Lille cedex, NORD Pas-de-calais, France, 59037
        • Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez
  • Germany
    • Baden-wuerttemberg
      • Villingen-Schwenningen, Baden-wuerttemberg, Germany, 78052
        • Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH
    • Hessen
      • Kassel, Hessen, Germany, 34119
        • Gemeinschaftspraxis Dres. Söling Und Siehl
  • Hungary
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem
    • Hajdu-bihar
      • Debrecen, Hajdu-bihar, Hungary, 4032
        • Debreceni Egyetem Orvos-es Egészsegtudomanyi Centrum
    • Somogy
      • Kaposvár, Somogy, Hungary, 7400
        • Somogy Megyei Kaposi Mor Oktato Korhaz
    • VAS
      • Szombathely, VAS, Hungary, 9700
        • Markusovszky Egyetemi Oktatókórház
  • Israel
      • Jerusalem, Israel, 91120
        • Hadassah Medical Organization, Ein Kerem
      • Petach Tikva, Israel, 49100
        • Rabin Medical Center
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
      • Novara, Italy, 28100
        • Azienda Ospedaliero Universitaria (AOU) "Maggiore della Carita" di Novara
      • Pesaro, Italy, 61100
        • Azienda Ospedaliera Ospedali Riuniti Marche Nord
      • Pordenone, Italy, 33081
        • Centro di Riferimento Oncologico di Aviano
      • Torino, Italy, 10126
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino
  • Japan
    • Aichi
      • Nagoya, Aichi, Japan, 464-8681
        • Aichi Cancer Center Hospital
      • Nagoya City, Aichi, Japan, 467-8681
        • Nagoya City University Hospital
      • Nagoya-shi, Aichi, Japan, 4600001
        • National Hospital Organization Nagoya Medical Center
    • Fukuoka
      • Minami Ku, Fukuoka, Japan, 811-1395
        • National Hospital Organization Kyushu Cancer Center
    • Hyogo
      • Kobe-city, Hyogo, Japan, 650-0047
        • Kobe City Medical Center General Hospital
    • Kanagawa
      • Isehara-shi, Kanagawa, Japan, 259-1193
        • Tokai University Hospital
    • Kumamoto
      • Chuo-ku, Kumamoto, Japan, 860-0008
        • National Hospital Organization Kumamoto Medical Center
    • Miyagi
      • Sendai, Miyagi, Japan, 9808574
        • Tohoku University Hospital
    • Okayama
      • Okayama-city, Okayama, Japan, 700-8558
        • Okayama University Hospital
    • Osaka
      • Osaka-shi, Osaka, Japan, 545-8586
        • Osaka City University Hospital
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 1040045
        • National Cancer Center Hospital
      • Koto-ku, Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital of JFCR
      • Minato-ku, Tokyo, Japan, 1058470
        • Toranomon Hospital
  • Korea, Republic of
      • Seoul, Korea, Republic of, 135-710
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 138-876
        • Asan Medical Center
  • Poland
      • Kraków, Poland, 30-510
        • Malopolskie Centrum Medyczne s.c.
      • Olsztyn, Poland, 10-228
        • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim
      • Warszawa, Poland, 02-781
        • Centrum Onkologii i Hipertermii
  • Portugal
      • Porto, Portugal, 4099-001
        • Hospital Geral de Santo António do Centro Hospitalar do Porto
  • Romania
      • Bucuresti, Romania, 022328
        • Institutul Clinic Fundeni
  • Russian Federation
      • Ekaterinburg, Russian Federation, 620102
        • Sverdlovsk Regional Clinical Hospital #1
      • Nizhniy Novgorod, Russian Federation, 603126
        • Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko
      • Ryazan, Russian Federation, 390039
        • Ryazan Regional Clinical Hospital
      • Saint Petersburg, Russian Federation, 197341
        • FSI "V.A. Almazov Federal Centre of Heart, Blood and Endocrinology of Rosmedtechnologies"
      • Saint-Petersburg, Russian Federation, 197022
        • Saint Petersburg I.P. Pavlov State Medical University
      • Saratov, Russian Federation, 410 028
        • Saratov State Medical University
  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital
      • Singapore, Singapore, 169610
        • National Cancer Centre Singapore
      • Singapore, Singapore, 258500
        • Gleneagles Medical Centre
  • Spain
      • Badalona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro
  • Sweden
      • Malmö, Sweden, 205 02
        • Skånes Universitetssjukhus, Malmö
  • Taiwan
      • Kaohsiung, Taiwan, 83301
        • Chang Gung Memorial Hospital (CGMH)
      • Taipei, Taiwan, 11490
        • Tri-Service General Hospital
  • United Kingdom
      • Middlesex, United Kingdom, HA6 2RN
        • Mount Vernon Hospital
      • Sunderland, United Kingdom, SR4 7TP
        • Sunderland Royal Infirmary
    • England
      • London, England, United Kingdom, EC1A 7BE
        • Barts and the London NHS Trust
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35805
        • Clearview Cancer Institute
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Cancer and Research Center
    • California
      • Duarte, California, United States, 91010
        • City of Hope Cancer Center
      • Fullerton, California, United States, 92835
        • Saint Jude Heritage Healthcare
      • Long Beach, California, United States, 90813
        • Pacific Shores Medical Group
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Redondo Beach, California, United States, 90277
        • Cancer Care Associates
      • Santa Barbara, California, United States, 93105
        • Cancer Center of Santa Barbara
      • Santa Maria, California, United States, 93454
        • Central Coast Medical Oncology Group
    • Connecticut
      • Middletown, Connecticut, United States, 06457
        • Middlesex Hospital Cancer Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Fort Myers, Florida, United States, 33916
        • Florida Cancer Specialists and Research Institute
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State University
    • Nevada
      • Las Vegas, Nevada, United States, 89169-3321
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • New York, New York, United States, 10065
        • Weill Cornell Medical College
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Middletown, Ohio, United States, 45042
        • Signal Point Clinical Research Center, LLC
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Perelman Center for Advanced Medicine
    • South Dakota
      • Watertown, South Dakota, United States, 57252
        • Prairie Lakes Healthcare System
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology, PLLC
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Cancer Center
    • Texas
      • Bedford, Texas, United States, 76022
        • Texas Oncology, P.A.
      • Fort Sam Houston, Texas, United States, 78234
        • Brooke Army Medical Center
      • Fort Worth, Texas, United States, 76104
        • Center for Cancer and Blood Disorders, PC
    • Virginia
      • Winchester, Virginia, United States, 22601
        • Shenandoah Oncology Associates, PC
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center
      • Tacoma, Washington, United States, 98405
        • Northwest Medical Specialties, PLLC
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital and Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab + idelalisib
Participants will receive rituximab + idelalisib.
Drug: Rituximab
375 mg/m^2 administered intravenously weekly for 4 weeks, then every 8 weeks (up to a total of 8 infusions)
Other Names:
  • Rituxan®
  • MabThera®
Drug: Idelalisib
150 mg tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
Placebo Comparator: Rituximab + Placebo
Participants will receive rituximab + placebo. Following confirmation of iNHL disease progression by the independent review committee and unblinding, participants may be eligible to receive open-label idelalisib 150 mg twice daily.
Drug: Rituximab
375 mg/m^2 administered intravenously weekly for 4 weeks, then every 8 weeks (up to a total of 8 infusions)
Other Names:
  • Rituxan®
  • MabThera®
Drug: Idelalisib
150 mg tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
Drug: Placebo
Tablets administered orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
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 Outcome Measures

Outcome Measure
Measure Description
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.
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.
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.
Overall Survival
Overall survival is defined as the interval from randomization to death from any cause.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 16, 2013

Primary Completion (Actual)

May 18, 2016

Study Completion (Actual)

May 18, 2016

Study Registration Dates

First Submitted

November 14, 2012

First Submitted That Met QC Criteria

November 19, 2012

First Posted (Estimate)

November 26, 2012

Study Record Updates

Last Update Posted (Actual)

November 16, 2018

Last Update Submitted That Met QC Criteria

October 19, 2018

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-313-0124

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

IPD Sharing Time Frame

18 months after study completion

IPD Sharing Access Criteria

A secured external environment with username, password, and RSA code.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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