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

Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT01732913
Collaborator
(none)
295
Enrollment
103
Locations
2
Arms
40
Actual Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
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 :
Jan 16, 2013
Actual Primary Completion Date :
May 18, 2016
Actual Study Completion Date :
May 18, 2016

Arms and Interventions

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®

    		•

    Outcome Measures

    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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01732913
    Other Study ID Numbers:
    • GS-US-313-0124
    First Posted:
    Nov 26, 2012
    Last Update Posted:
    Nov 16, 2018
    Last Verified:
    Mar 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Lymphoma
    Lymphoma, Non-Hodgkin
    Rituximab
    Idelalisib

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the North America, Europe, and Asia Pacific. The first participant was screened on 16 January 2013. The last study visit occurred on 18 May 2016.
    Pre-assignment Detail 385 participants were screened.
    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab
    Arm/Group Description Idelalisib (Zydelig®) 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions
    Period Title: Overall Study
    STARTED 198 97
    COMPLETED 42 28
    NOT COMPLETED 156 69

    Baseline Characteristics

    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab Total
    Arm/Group Description Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Total of all reporting groups
    Overall Participants 198 97 295
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64
    (11.4)
    67
    (11.4)
    65
    (11.4)
    Sex: Female, Male (Count of Participants)
    Female
    99
    50%
    48
    49.5%
    147
    49.8%
    Male
    99
    50%
    49
    50.5%
    148
    50.2%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    35
    17.7%
    17
    17.5%
    52
    17.6%
    Black or African American
    5
    2.5%
    4
    4.1%
    9
    3.1%
    White
    123
    62.1%
    54
    55.7%
    177
    60%
    Other
    3
    1.5%
    3
    3.1%
    6
    2%
    Not Permitted
    32
    16.2%
    19
    19.6%
    51
    17.3%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    12
    6.1%
    3
    3.1%
    15
    5.1%
    Not Hispanic or Latino
    150
    75.8%
    75
    77.3%
    225
    76.3%
    Unknown or Not Reported
    36
    18.2%
    19
    19.6%
    55
    18.6%
    Region of Enrollment (Count of Participants)
    Russian Federation
    7
    3.5%
    2
    2.1%
    9
    3.1%
    Singapore
    5
    2.5%
    4
    4.1%
    9
    3.1%
    Romania
    1
    0.5%
    0
    0%
    1
    0.3%
    Hungary
    24
    12.1%
    6
    6.2%
    30
    10.2%
    United States
    65
    32.8%
    34
    35.1%
    99
    33.6%
    Japan
    23
    11.6%
    9
    9.3%
    32
    10.8%
    United Kingdom
    3
    1.5%
    1
    1%
    4
    1.4%
    Portugal
    3
    1.5%
    1
    1%
    4
    1.4%
    Spain
    6
    3%
    0
    0%
    6
    2%
    Czech Republic
    2
    1%
    0
    0%
    2
    0.7%
    Sweden
    6
    3%
    2
    2.1%
    8
    2.7%
    Taiwan
    1
    0.5%
    1
    1%
    2
    0.7%
    Poland
    5
    2.5%
    7
    7.2%
    12
    4.1%
    Korea, Republic of
    4
    2%
    2
    2.1%
    6
    2%
    Italy
    7
    3.5%
    4
    4.1%
    11
    3.7%
    Israel
    3
    1.5%
    0
    0%
    3
    1%
    Australia
    7
    3.5%
    6
    6.2%
    13
    4.4%
    France
    25
    12.6%
    17
    17.5%
    42
    14.2%
    Germany
    1
    0.5%
    1
    1%
    2
    0.7%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival
    Description 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).
    Time Frame

    Outcome Measure Data

    Analysis Population Description
    Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab
    Arm/Group Description Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions
    Measure Participants 0 0
    2. Secondary Outcome
    Title Overall Response Rate
    Description 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.
    Time Frame

    Outcome Measure Data

    Analysis Population Description
    Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab
    Arm/Group Description Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions
    Measure Participants 0 0
    3. Secondary Outcome
    Title Lymph Node Response Rate
    Description 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.
    Time Frame

    Outcome Measure Data

    Analysis Population Description
    Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab
    Arm/Group Description Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions
    Measure Participants 0 0
    4. Secondary Outcome
    Title Complete Response Rate
    Description 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.
    Time Frame

    Outcome Measure Data

    Analysis Population Description
    Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.
    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab
    Arm/Group Description Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions
    Measure Participants 0 0
    5. Secondary Outcome
    Title Overall Survival
    Description Overall survival is defined as the interval from randomization to death from any cause.
    Time Frame

    Outcome Measure Data

    Analysis Population Description
    Due to the early termination of the study, efficacy data were not mature for all participants, and therefore the prespecified analyses were not conducted.
    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab
    Arm/Group Description Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions
    Measure Participants 0 0

    Adverse Events

    Time Frame Up to 27 months plus 30 days
    Adverse Event Reporting Description Safety Analysis Set
    Arm/Group Title Idelalisib + Rituximab Placebo + Rituximab
    Arm/Group Description Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions Placebo tablet orally twice daily + rituximab 375 mg/m^2 intravenously starting on Day 1 for a total of 8 infusions
    All Cause Mortality
    Idelalisib + Rituximab Placebo + Rituximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Idelalisib + Rituximab Placebo + Rituximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 103/198 (52%) 11/95 (11.6%)
    Blood and lymphatic system disorders
    Anaemia 1/198 (0.5%) 0/95 (0%)
    Febrile neutropenia 7/198 (3.5%) 0/95 (0%)
    Leukopenia 1/198 (0.5%) 0/95 (0%)
    Neutropenia 3/198 (1.5%) 0/95 (0%)
    Thrombocytopenia 1/198 (0.5%) 1/95 (1.1%)
    Cardiac disorders
    Acute coronary syndrome 1/198 (0.5%) 0/95 (0%)
    Atrial fibrillation 1/198 (0.5%) 0/95 (0%)
    Bradycardia 0/198 (0%) 1/95 (1.1%)
    Cardiac arrest 1/198 (0.5%) 0/95 (0%)
    Cardiac failure congestive 1/198 (0.5%) 2/95 (2.1%)
    Pericarditis 1/198 (0.5%) 0/95 (0%)
    Tachycardia 1/198 (0.5%) 0/95 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/198 (0.5%) 0/95 (0%)
    Colitis 8/198 (4%) 0/95 (0%)
    Colitis ulcerative 1/198 (0.5%) 0/95 (0%)
    Constipation 1/198 (0.5%) 0/95 (0%)
    Diarrhoea 18/198 (9.1%) 0/95 (0%)
    Enteritis 1/198 (0.5%) 0/95 (0%)
    Enterocolitis 1/198 (0.5%) 0/95 (0%)
    Incarcerated inguinal hernia 1/198 (0.5%) 0/95 (0%)
    Intestinal obstruction 0/198 (0%) 1/95 (1.1%)
    Nausea 1/198 (0.5%) 0/95 (0%)
    Pancreatitis 1/198 (0.5%) 0/95 (0%)
    Salivary gland disorder 0/198 (0%) 1/95 (1.1%)
    Salivary gland enlargement 0/198 (0%) 1/95 (1.1%)
    Stomatitis 1/198 (0.5%) 0/95 (0%)
    Vomiting 3/198 (1.5%) 0/95 (0%)
    General disorders
    Asthenia 2/198 (1%) 0/95 (0%)
    Death 1/198 (0.5%) 0/95 (0%)
    Fatigue 1/198 (0.5%) 1/95 (1.1%)
    Gait disturbance 1/198 (0.5%) 0/95 (0%)
    Oedema 1/198 (0.5%) 0/95 (0%)
    Pyrexia 9/198 (4.5%) 1/95 (1.1%)
    Hepatobiliary disorders
    Cholecystitis acute 1/198 (0.5%) 0/95 (0%)
    Drug-induced liver injury 3/198 (1.5%) 0/95 (0%)
    Hepatic failure 1/198 (0.5%) 0/95 (0%)
    Hepatic function abnormal 2/198 (1%) 0/95 (0%)
    Jaundice 2/198 (1%) 0/95 (0%)
    Immune system disorders
    Hypersensitivity 1/198 (0.5%) 0/95 (0%)
    Infections and infestations
    Bronchitis 1/198 (0.5%) 0/95 (0%)
    Cellulitis 1/198 (0.5%) 0/95 (0%)
    Clostridium difficile colitis 1/198 (0.5%) 0/95 (0%)
    Cytomegalovirus infection 2/198 (1%) 0/95 (0%)
    Eczema herpeticum 1/198 (0.5%) 0/95 (0%)
    Fungaemia 1/198 (0.5%) 0/95 (0%)
    Gastroenteritis 1/198 (0.5%) 0/95 (0%)
    Herpes zoster meningomyelitis 1/198 (0.5%) 0/95 (0%)
    Infection 1/198 (0.5%) 1/95 (1.1%)
    Infective exacerbation of chronic obstructive airways disease 1/198 (0.5%) 0/95 (0%)
    Lower respiratory tract infection 0/198 (0%) 1/95 (1.1%)
    Metapneumovirus infection 0/198 (0%) 1/95 (1.1%)
    Neutropenic sepsis 1/198 (0.5%) 0/95 (0%)
    Otitis externa 1/198 (0.5%) 0/95 (0%)
    Pneumocystis jirovecii pneumonia 1/198 (0.5%) 0/95 (0%)
    Pneumonia 19/198 (9.6%) 0/95 (0%)
    Sepsis 5/198 (2.5%) 0/95 (0%)
    Septic shock 1/198 (0.5%) 0/95 (0%)
    Skin bacterial infection 1/198 (0.5%) 0/95 (0%)
    Staphylococcal bacteraemia 1/198 (0.5%) 0/95 (0%)
    Upper respiratory tract infection 2/198 (1%) 0/95 (0%)
    Urinary tract infection 4/198 (2%) 0/95 (0%)
    Injury, poisoning and procedural complications
    Clavicle fracture 1/198 (0.5%) 0/95 (0%)
    Fall 1/198 (0.5%) 0/95 (0%)
    Infusion related reaction 1/198 (0.5%) 2/95 (2.1%)
    Laceration 1/198 (0.5%) 0/95 (0%)
    Rib fracture 1/198 (0.5%) 0/95 (0%)
    Spinal compression fracture 1/198 (0.5%) 0/95 (0%)
    Subdural haematoma 1/198 (0.5%) 0/95 (0%)
    Subdural haemorrhage 1/198 (0.5%) 0/95 (0%)
    Upper limb fracture 0/198 (0%) 1/95 (1.1%)
    Investigations
    Alanine aminotransferase increased 11/198 (5.6%) 0/95 (0%)
    Aspartate aminotransferase increased 10/198 (5.1%) 0/95 (0%)
    Blood alkaline phosphatase increased 0/198 (0%) 1/95 (1.1%)
    Blood creatinine increased 1/198 (0.5%) 0/95 (0%)
    Blood lactate dehydrogenase increased 1/198 (0.5%) 0/95 (0%)
    Transaminases increased 1/198 (0.5%) 0/95 (0%)
    Metabolism and nutrition disorders
    Cachexia 1/198 (0.5%) 0/95 (0%)
    Dehydration 4/198 (2%) 0/95 (0%)
    Hypercalcaemia 1/198 (0.5%) 0/95 (0%)
    Hyperglycaemia 1/198 (0.5%) 0/95 (0%)
    Hypoglycaemia 1/198 (0.5%) 0/95 (0%)
    Hypokalaemia 2/198 (1%) 0/95 (0%)
    Hyponatraemia 2/198 (1%) 0/95 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/198 (0.5%) 0/95 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer recurrent 0/198 (0%) 1/95 (1.1%)
    Glioblastoma 1/198 (0.5%) 0/95 (0%)
    Nervous system disorders
    Cerebrovascular accident 2/198 (1%) 0/95 (0%)
    Dizziness 2/198 (1%) 0/95 (0%)
    Syncope 3/198 (1.5%) 0/95 (0%)
    Transient ischaemic attack 3/198 (1.5%) 0/95 (0%)
    Psychiatric disorders
    Anxiety 1/198 (0.5%) 0/95 (0%)
    Major depression 1/198 (0.5%) 0/95 (0%)
    Mental status changes 2/198 (1%) 0/95 (0%)
    Suicidal ideation 1/198 (0.5%) 0/95 (0%)
    Renal and urinary disorders
    Acute kidney injury 5/198 (2.5%) 0/95 (0%)
    Nephrolithiasis 1/198 (0.5%) 0/95 (0%)
    Urinary retention 1/198 (0.5%) 0/95 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchitis chronic 1/198 (0.5%) 0/95 (0%)
    Chronic obstructive pulmonary disease 2/198 (1%) 0/95 (0%)
    Cough 1/198 (0.5%) 0/95 (0%)
    Dyspnoea 3/198 (1.5%) 0/95 (0%)
    Dyspnoea exertional 1/198 (0.5%) 0/95 (0%)
    Hypoxia 2/198 (1%) 0/95 (0%)
    Interstitial lung disease 1/198 (0.5%) 0/95 (0%)
    Lung disorder 2/198 (1%) 0/95 (0%)
    Pneumonitis 8/198 (4%) 0/95 (0%)
    Pulmonary embolism 3/198 (1.5%) 0/95 (0%)
    Respiratory failure 1/198 (0.5%) 0/95 (0%)
    Skin and subcutaneous tissue disorders
    Psoriasis 2/198 (1%) 0/95 (0%)
    Rash 4/198 (2%) 0/95 (0%)
    Other (Not Including Serious) Adverse Events
    Idelalisib + Rituximab Placebo + Rituximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 189/198 (95.5%) 83/95 (87.4%)
    Blood and lymphatic system disorders
    Anaemia 12/198 (6.1%) 6/95 (6.3%)
    Neutropenia 25/198 (12.6%) 5/95 (5.3%)
    Gastrointestinal disorders
    Abdominal pain 20/198 (10.1%) 4/95 (4.2%)
    Constipation 28/198 (14.1%) 13/95 (13.7%)
    Diarrhoea 88/198 (44.4%) 18/95 (18.9%)
    Gastrooesophageal reflux disease 10/198 (5.1%) 3/95 (3.2%)
    Nausea 50/198 (25.3%) 12/95 (12.6%)
    Vomiting 29/198 (14.6%) 7/95 (7.4%)
    General disorders
    Asthenia 15/198 (7.6%) 9/95 (9.5%)
    Chills 11/198 (5.6%) 4/95 (4.2%)
    Fatigue 41/198 (20.7%) 20/95 (21.1%)
    Oedema peripheral 14/198 (7.1%) 5/95 (5.3%)
    Pyrexia 50/198 (25.3%) 11/95 (11.6%)
    Infections and infestations
    Bronchitis 9/198 (4.5%) 6/95 (6.3%)
    Nasopharyngitis 10/198 (5.1%) 6/95 (6.3%)
    Upper respiratory tract infection 23/198 (11.6%) 8/95 (8.4%)
    Urinary tract infection 13/198 (6.6%) 3/95 (3.2%)
    Injury, poisoning and procedural complications
    Infusion related reaction 36/198 (18.2%) 20/95 (21.1%)
    Investigations
    Alanine aminotransferase increased 65/198 (32.8%) 0/95 (0%)
    Aspartate aminotransferase increased 56/198 (28.3%) 0/95 (0%)
    Gamma-glutamyltransferase increased 11/198 (5.6%) 1/95 (1.1%)
    Transaminases increased 12/198 (6.1%) 1/95 (1.1%)
    Weight decreased 20/198 (10.1%) 1/95 (1.1%)
    Metabolism and nutrition disorders
    Decreased appetite 26/198 (13.1%) 2/95 (2.1%)
    Dehydration 11/198 (5.6%) 0/95 (0%)
    Hypokalaemia 21/198 (10.6%) 4/95 (4.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 9/198 (4.5%) 6/95 (6.3%)
    Back pain 9/198 (4.5%) 6/95 (6.3%)
    Pain in extremity 16/198 (8.1%) 3/95 (3.2%)
    Nervous system disorders
    Dizziness 12/198 (6.1%) 6/95 (6.3%)
    Headache 30/198 (15.2%) 12/95 (12.6%)
    Psychiatric disorders
    Anxiety 10/198 (5.1%) 3/95 (3.2%)
    Insomnia 21/198 (10.6%) 11/95 (11.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 28/198 (14.1%) 14/95 (14.7%)
    Dyspnoea 12/198 (6.1%) 2/95 (2.1%)
    Oropharyngeal pain 12/198 (6.1%) 3/95 (3.2%)
    Skin and subcutaneous tissue disorders
    Pruritus 25/198 (12.6%) 4/95 (4.2%)
    Rash 38/198 (19.2%) 12/95 (12.6%)
    Rash maculo-papular 16/198 (8.1%) 2/95 (2.1%)
    Vascular disorders
    Hypertension 12/198 (6.1%) 2/95 (2.1%)

    Limitations/Caveats

    Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Clinical Trial Disclosures
    Organization Gilead Sciences
    Phone
    Email ClinicalTrialDisclosures@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01732913
    Other Study ID Numbers:
    • GS-US-313-0124
    First Posted:
    Nov 26, 2012
    Last Update Posted:
    Nov 16, 2018
    Last Verified:
    Mar 1, 2017