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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01732913
Recruitment Status : Terminated
First Posted : November 26, 2012
Results First Posted : May 11, 2017
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief 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).


Condition or disease Intervention/treatment Phase
Indolent Non-Hodgkin's Lymphomas Drug: Placebo Drug: Rituximab Drug: Idelalisib Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 295 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : January 16, 2013
Actual Primary Completion Date : May 18, 2016
Actual Study Completion Date : May 18, 2016


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:
  • GS-1101
  • CAL-101
  • Zydelig®

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: Placebo
Tablets administered orally 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:
  • GS-1101
  • CAL-101
  • Zydelig®




Primary Outcome Measures :
  1. 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 :
  1. 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.

  2. 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.

  3. 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.

  4. Overall Survival
    Overall survival is defined as the interval from randomization to death from any cause.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01732913


Locations
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United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States, 35805
United States, Arizona
Ironwood Cancer and Research Center
Chandler, Arizona, United States, 85224
United States, California
City of Hope Cancer Center
Duarte, California, United States, 91010
Saint Jude Heritage Healthcare
Fullerton, California, United States, 92835
Pacific Shores Medical Group
Long Beach, California, United States, 90813
UCLA Medical Center
Los Angeles, California, United States, 90095
Cancer Care Associates
Redondo Beach, California, United States, 90277
Cancer Center of Santa Barbara
Santa Barbara, California, United States, 93105
Central Coast Medical Oncology Group
Santa Maria, California, United States, 93454
United States, Connecticut
Middlesex Hospital Cancer Center
Middletown, Connecticut, United States, 06457
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Florida Cancer Specialists and Research Institute
Fort Myers, Florida, United States, 33916
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Kansas
Cancer Center of Kansas
Wichita, Kansas, United States, 67214
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169-3321
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Weill Cornell Medical College
New York, New York, United States, 10065
United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Signal Point Clinical Research Center, LLC
Middletown, Ohio, United States, 45042
United States, Pennsylvania
Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, United States, 19104
United States, South Dakota
Prairie Lakes Healthcare System
Watertown, South Dakota, United States, 57252
United States, Tennessee
Tennessee Oncology, PLLC
Chattanooga, Tennessee, United States, 37404
Sarah Cannon Cancer Center
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology, P.A.
Bedford, Texas, United States, 76022
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
Center for Cancer and Blood Disorders, PC
Fort Worth, Texas, United States, 76104
United States, Virginia
Shenandoah Oncology Associates, PC
Winchester, Virginia, United States, 22601
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Northwest Medical Specialties, PLLC
Tacoma, Washington, United States, 98405
United States, Wisconsin
Froedtert Hospital and Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, Queensland
Haematology and Oncology Clinics of Australia at Chermside
Milton, Queensland, Australia, 4064
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
Monash Medical Centre
Clayton, Victoria, Australia, 3168
Saint Vincent's Hospital
Fitzroy, Victoria, Australia, 3065
Western Hospital
Footscray, Victoria, Australia, 3011
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Australia
Adelaide Cancer Centre
Kurralta Park, Australia, SA 5037
Fiona Stanley Hospital
Murdoch, Australia, 6150
Czechia
Fakultní nemocnice Hradec Králové
Hradec Králové, Czechia, 500 05
France
University Hospital of Bordeaux
Pessac, Aquitaine, France, 33604
Hôpital Necker-Enfants Malades
Paris, Ile-de-france, France, 75015
Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez
Lille cedex, NORD Pas-de-calais, France, 59037
Centre Hospitalier Universitaire Brest
Brest, France, 29609
Centre Hospitalier de Dunkerque
Dunkerque, France, 59385
Centre Hospitalier de Versailles
Le Chesnay, France, 78157
Centre Léon Bérard
Lyon Cedex 08, France, 69373
Hôpital Hôtel-Dieu
Nantes cedex 1, France, 44093
Centre Hospitalier Lyon Sud
Pierre Bénite Cedex, France, 69495
Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie
Poitiers Cedex, France, 86000
Germany
Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH
Villingen-Schwenningen, Baden-wuerttemberg, Germany, 78052
Gemeinschaftspraxis Dres. Söling Und Siehl
Kassel, Hessen, Germany, 34119
Hungary
Debreceni Egyetem Orvos-és Egészségtudományi Centrum
Debrecen, Hajdu-bihar, Hungary, 4032
Somogy Megyei Kaposi Mór Oktató Kórház
Kaposvár, Somogy, Hungary, 7400
Markusovszky Egyetemi Oktatókórház
Szombathely, VAS, Hungary, 9700
Semmelweis Egyetem
Budapest, Hungary, 1083
Országos Onkológiai Intézet
Budapest, Hungary, 1122
Israel
Hadassah Medical Organization, Ein Kerem
Jerusalem, Israel, 91120
Rabin Medical Center
Petach Tikva, Israel, 49100
Italy
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria (AOU) "Maggiore della Carita" di Novara
Novara, Italy, 28100
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro, Italy, 61100
Centro di Riferimento Oncologico di Aviano
Pordenone, Italy, 33081
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, Italy, 10126
Japan
Nagoya City University Hospital
Nagoya City, Aichi, Japan, 467-8681
National Hospital Organization Nagoya Medical Center
Nagoya-shi, Aichi, Japan, 4600001
Aichi Cancer Center Hospital
Nagoya, Aichi, Japan, 464-8681
National Hospital Organization Kyushu Cancer Center
Minami Ku, Fukuoka, Japan, 811-1395
Kobe City Medical Center General Hospital
Kobe-city, Hyogo, Japan, 650-0047
Tokai University Hospital
Isehara-shi, Kanagawa, Japan, 259-1193
National Hospital Organization Kumamoto Medical Center
Chuo-ku, Kumamoto, Japan, 860-0008
Tohoku University Hospital
Sendai, Miyagi, Japan, 9808574
Okayama University Hospital
Okayama-city, Okayama, Japan, 700-8558
Osaka City University Hospital
Osaka-shi, Osaka, Japan, 545-8586
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan, 1040045
The Cancer Institute Hospital of JFCR
Koto-ku, Tokyo, Japan, 135-8550
Toranomon Hospital
Minato-ku, Tokyo, Japan, 1058470
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Asan Medical Center
Seoul, Korea, Republic of, 138-876
Poland
Malopolskie Centrum Medyczne S.C.
Kraków, Poland, 30-510
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim
Olsztyn, Poland, 10-228
Centrum Onkologii i Hipertermii
Warszawa, Poland, 02-781
Portugal
Hospital Geral de Santo António do Centro Hospitalar do Porto
Porto, Portugal, 4099-001
Romania
Institutul Clinic Fundeni
Bucuresti, Romania, 022328
Russian Federation
Sverdlovsk Regional Clinical Hospital #1
Ekaterinburg, Russian Federation, 620102
Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko
Nizhniy Novgorod, Russian Federation, 603126
Ryazan Regional Clinical Hospital
Ryazan, Russian Federation, 390039
FSI "V.A. Almazov Federal Centre of Heart, Blood and Endocrinology of Rosmedtechnologies"
Saint Petersburg, Russian Federation, 197341
Saint Petersburg I.P. Pavlov State Medical University
Saint-Petersburg, Russian Federation, 197022
Saratov State Medical University
Saratov, Russian Federation, 410 028
Singapore
Singapore General Hospital
Singapore, Singapore, 169608
National Cancer Centre Singapore
Singapore, Singapore, 169610
Gleneagles Medical Centre
Singapore, Singapore, 258500
Spain
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, Spain, 28222
Hospital Universitari Germans Trias i Pujol
Badalona, Spain, 08916
Sweden
Skånes Universitetssjukhus, Malmö
Malmö, Sweden, 205 02
Taiwan
Chang Gung Memorial Hospital (CGMH)
Kaohsiung, Taiwan, 83301
Tri-Service General Hospital
Taipei, Taiwan, 11490
United Kingdom
Barts and The London NHS Trust
London, England, United Kingdom, EC1A 7BE
Mount Vernon Hospital
Middlesex, United Kingdom, HA6 2RN
Sunderland Royal Infirmary
Sunderland, United Kingdom, SR4 7TP
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01732913    
Other Study ID Numbers: GS-US-313-0124
First Posted: November 26, 2012    Key Record Dates
Results First Posted: May 11, 2017
Last Update Posted: November 16, 2018
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
iNHL
indolent NHL
follicular lymphoma
CAL-101
Rituximab
Small lymphocytic lymphoma
lymphoplasmacytoid lymphoma
Waldenstrom macroglobulinemia
LPL
WM
Marginal zone lymphoma
MZL
SLL
FL
GS-1101
idelalisib
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Idelalisib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action