NCT01732926

Brief 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).

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
475

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2013

Typical duration for phase_3

Geographic Reach
15 countries

144 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 14, 2012

Completed
12 days until next milestone

First Posted

Study publicly available on registry

November 26, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

January 2, 2013

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 17, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 17, 2016

Completed
12 months until next milestone

Results Posted

Study results publicly available

May 11, 2017

Completed
Last Updated

November 16, 2018

Status Verified

March 1, 2017

Enrollment Period

3.4 years

First QC Date

November 14, 2012

Results QC Date

March 30, 2017

Last Update Submit

October 19, 2018

Conditions

Keywords

iNHLindolent NHLfollicular lymphomaCAL-101rituximabbendamustinesmall lymphocytic lymphomalymphoplasmacytoid lymphomaWaldenstrom macroglobulinemiaLPLWMMarginal zone lymphomaMZLSLLFLGS-1101PI3K inhibitoridelalisib

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Complete Response Rate (CR)

  • Overall Response Rate (ORR)

  • Lymph Node Response Rate

  • Overall Survival (OS)

Study Arms (2)

Rituximab + Bendamustine + Idelalisib

EXPERIMENTAL

Participants will receive rituximab + bendamustine + idelalisib.

Drug: IdelalisibDrug: RituximabDrug: Bendamustine

Rituximab + Bendamustine + Placebo

EXPERIMENTAL

Participants will receive rituximab + bendamustine + placebo.

Drug: RituximabDrug: BendamustineDrug: Placebo

Interventions

150 mg tablet administered orally twice daily

Also known as: Zydelig®, CAL-101, GS-1101
Rituximab + Bendamustine + Idelalisib

375 mg/m\^2 single-use vials administered intravenously every 4 weeks (up to a total of 6 infusions)

Also known as: Rituxan®, MabThera®
Rituximab + Bendamustine + IdelalisibRituximab + Bendamustine + Placebo

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)

Also known as: Treanda®
Rituximab + Bendamustine + IdelalisibRituximab + Bendamustine + Placebo

Tablet administered orally twice daily

Rituximab + Bendamustine + Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following
  • Follicular lymphoma (FL) Grade 1, 2, or 3a
  • Small lymphocytic lymphoma (SLL)
  • Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
  • Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (144)

Clearview Cancer Institute

Huntsville, Alabama, 35805, United States

Location

Ironwood Cancer and Research Center

Chandler, Arizona, 85224, United States

Location

Comprehensive Blood and Cancer Center (Bakersfield)

Bakersfield, California, 93309, United States

Location

Saint Jude Heritage Healthcare (TORI)

Fullerton, California, 92835, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

Cancer Care Associates

Redondo Beach, California, 90277, United States

Location

San Luis Obispo Oncology and Hematology

San Luis Obispo, California, 93401, United States

Location

Cancer Center of Santa Barbara

Santa Barbara, California, 93105, United States

Location

Central Coast Medical Oncology Group

Santa Maria, California, 93454, United States

Location

St Joseph Heritage Healthcare System

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente Vallejo Medical Center

Vallejo, California, 94589, United States

Location

Sylvester Comprehensive Cancer Center/UMHC

Deerfield Beach, Florida, 33442, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

Northwest Georgia Oncology Centers, PC

Marietta, Georgia, 30060, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Joliet Oncology Hematology Associates Ltd.

Joliet, Illinois, 60435, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

North Shore Hematology/Oncology Associates

East Setauket, New York, 11733, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Signal Point Clinical Research Center, LLC

Middletown, Ohio, 45042, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Bon Secours Saint Francis Hospital

Greenville, South Carolina, 29607, United States

Location

Texas Oncology, P.A.

Bedford, Texas, 76022, United States

Location

Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology, P.A.

Denton, Texas, 76210, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Texas Oncology, P.A.

Harlingen, Texas, 78550-8321, United States

Location

Texas Oncology, P.A.

Weslaco, Texas, 78596-6608, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

Northwest Medical Specialists

Tacoma, Washington, 98405, United States

Location

Aurora BayCare Medical Center

Green Bay, Wisconsin, 54308, United States

Location

Froedtert Hospital and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Haematology and Oncology Clinics of Australia Gold Coast

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Adelaide Cancer Centre

Kurralta Park, South Australia, 5037, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Saint Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Western Hospital

Footscray, Victoria, 3011, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 2T9, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Fraser Clinical Trials, Inc.

New Westminster, British Columbia, V3L 3W4, Canada

Location

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Queen Elizabeth II Health Sciences Centre, Centre for Clinical Research

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Hôpital Charles Lemoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3JI, Canada

Location

Centre Hospitalier Affilie Universitaire de Quebec

Québec, Quebec, G1J 1Z4, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

CancerCare Manitoba

Winnipeg, R3E 0V9, Canada

Location

Fakultní Nemocnice Ostrava

Ostrava - Poruba, Severomoravsky KRAJ, 708 52, Czechia

Location

Fakultní nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultní nemocnice Hradec Králové

Hradec Králové, 500 05, Czechia

Location

CHR Metz

Metz, Alsace, 57085, France

Location

Centre Hospitalier Universitaire de Strasbourg - Hôpital Hautepierre

Strasbourg, Alsace, 67098, France

Location

Institut Bergonié

Bordeaux, Aquitaine, 33076, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Centre Henri-Becquerel

Rouen, Haute-normandie, 76038, France

Location

Centre Jean Bernard

Le Mans, Pays de la Loire Region, 72000, France

Location

Centre Hospitalier Universitaire Brest

Brest, 29609, France

Location

Centre Hospitalier de Dunkerque

Dunkirk, 59385, France

Location

Centre Hospitalier Départmental La Roche sur Yon

La Roche-sur-Yon, 85925, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Hôpital Hôtel-Dieu

Nantes, 44093, France

Location

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86021, France

Location

Centre Hospitalier Régional et Universitaire - Hôpital Bretonneau

Tours, 37044, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Hôpital Necker-Enfants Malades

Paris, Île-de-France Region, 75015, France

Location

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

Villingen-Schwenningen, Baden-Wurttemberg, 78054, Germany

Location

Gemeinschaftspraxis Dres. Söling Und Siehl

Kassel, Hesse, 34117, Germany

Location

Vivantes Klinikum am Urban

Berlin, 10967, Germany

Location

Charite - Campus Virchow

Berlin, 13353, Germany

Location

Klinikum der Ludwig-Maximilians-Universität München

München, 81377, Germany

Location

Barzilai Medical Center

Ashkelon, 78278, Israel

Location

Soroka University Medical Center

Beersheba, 84101, Israel

Location

Rambam Health Corp.

Haifa, 31096, Israel

Location

Hadassah Medical Organization, Ein Kerem

Jerusalem, 91120, Israel

Location

Centro di Riferimento Oncologico di Aviano

Aviano, 33081, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Spedali Civili Di Brescia Azienda Ospedaliera

Brescia, 25123, Italy

Location

IRCCS Azienda Ospedaliera Universitaria San Martino

Genova, 16132, Italy

Location

Ospedale San Raffaele-IRCCS

Milan, 20132, Italy

Location

Azienda Ospedaliera Ospedale Niguarda Ca' Granda

Milan, 20162, Italy

Location

Azienda Ospedaliero Universitaria (AOU) "Maggiore della Carita" di Novara

Novara, 28100, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, 61122, Italy

Location

Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto

Piacenza, 29100, Italy

Location

Azienda Ospedaliera Universitaria Senese - Policlinico S. Maria alle Scotte

Siena, 53100, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Malopolskie Centrum Medyczne S.C.

Krakow, 30-510, Poland

Location

Wojewódzki Szpital Specjalistyczny im. Mikolaja Kopernika w Lodzi

Lódz, 93-510, Poland

Location

Szpital Kliniczny nr 1, Katedra i Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, 20-081, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim

Olsztyn, 10-228, Poland

Location

Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku

Słupsk, 76-200, Poland

Location

Centralny Szpital Kliniczny MSW w Warszawie

Warsaw, 02-507, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Centrum Onkologii i Hipertermii

Warsaw, 02-781, Poland

Location

N. N. Blokhin Russian Cancer Research Center

Moscow, 115478, Russia

Location

Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko

Nizhny Novgorod, 603126, Russia

Location

Ryazan Regional Clinical Hospital

Ryazan, 390039, Russia

Location

FGU Russian Scientific Research Institute of Hematology and Transfusiology

Saint Petersburg, 191024, Russia

Location

Saint Petersburg I.P. Pavlov State Medical University

Saint Petersburg, 197022, Russia

Location

FSI "V.A. Almazov Federal Centre of Heart, Blood and Endocrinology of Rosmedtechnologies"

Saint Petersburg, 197341, Russia

Location

Saratov State Medical University

Saratov, 140012, Russia

Location

State Budgetary Healthcare Institution "Volgograd Regional Clinical Oncology Dispensary #1"

Volgograd, 400138, Russia

Location

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, 620102, Russia

Location

Central City Hospital # 7

Yekaterinburg, 620137, Russia

Location

Dong-A University Medical Center

Busan, 602-715, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Universitario La Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, 38320, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fé de Valencia

Valencia, 46026, Spain

Location

Karolinska Universitetssjukhuset

Huddinge, Stockholm County, 141 86, Sweden

Location

Länssjukhuset Ryhov

Jönköping, 551 85, Sweden

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Kent and Canterbury Hospital

Canterbury, England, CT1 3NG, United Kingdom

Location

University Hospital Coventry

Coventry, England, CV2 2DX, United Kingdom

Location

Royal Bournemouth General Hospital

Dorset, England, BH7 7DW, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, England, LS9 7TF, United Kingdom

Location

Barts and The London NHS Trust

London, England, EC1M 6BQ, United Kingdom

Location

University College London Hospitals National Health Society Foundation Trust

London, England, NW1 2PG, United Kingdom

Location

Guys and Saint Thomas NHS Foundation Trust

London, England, SE1 9RT, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, England, W12 0NN, United Kingdom

Location

Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

Location

Christie Hospital NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, England, OX3 7LE, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Mount Vernon Hospital

Middlesex, HA6 2RN, United Kingdom

Location

New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, FollicularLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal Zone

Interventions

idelalisibRituximabBendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Limitations and 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.

Results Point of Contact

Title
Clinical Trial Disclosures
Organization
Gilead Sciences

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 14, 2012

First Posted

November 26, 2012

Study Start

January 2, 2013

Primary Completion

May 17, 2016

Study Completion

May 17, 2016

Last Updated

November 16, 2018

Results First Posted

May 11, 2017

Record last verified: 2017-03

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
18 months after study completion
Access Criteria
A secured external environment with username, password, and RSA code.
More information

Locations