A Randomized, Double-Blind and Placebo-Controlled Study of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela)

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. Identifier: NCT01569295
Recruitment Status : Active, not recruiting
First Posted : April 3, 2012
Results First Posted : February 27, 2018
Last Update Posted : February 27, 2018
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 (IDL [GS-1101, Zydelig®]) to bendamustine + rituximab (BR) on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL)

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Idelalisib Drug: Rituximab Drug: Bendamustine Drug: Placebo to match idelalisib Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 416 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 Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia
Actual Study Start Date : June 26, 2012
Actual Primary Completion Date : October 7, 2015
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
Experimental: Idelalisib+bendamustine+rituximab
Participants will receive idelalisib plus bendamustine and rituximab
Drug: Idelalisib
Idelalisib 150 mg administered orally twice daily
Other Names:
  • GS-1101
  • CAL 101
  • CAL-101
  • Zydelig®

Drug: Rituximab
Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions
Other Names:
  • Rituxan®
  • MabThera

Drug: Bendamustine
Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions
Other Names:
  • Ribomustin
  • Treanda®

Placebo Comparator: Placebo to match idelalisib+bendamustine+rituximab
Participants will receive placebo to match idelalisib plus bendamustine and rituximab
Drug: Rituximab
Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions
Other Names:
  • Rituxan®
  • MabThera

Drug: Bendamustine
Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions
Other Names:
  • Ribomustin
  • Treanda®

Drug: Placebo to match idelalisib
Placebo to match idelalisib administered orally twice daily

Primary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: Up to 45 months ]
    Progression-free survival (PFS) was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. PFS (months) = (minimum (date of disease progression, date of death) - date of randomization + 1)/30.4375

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 45 months ]

    ORR was the percentage of participants who achieved a complete response (CR), CR with incomplete marrow recovery (CRi,) or partial response (PR) and maintained the response for at least 12 weeks. CR was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy.

    PR was defined as >1 of the following criteria: a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver size, spleen size; plus ≥ 1 of the following: ≥ 1500/μL absolute neutrophil count, > 100000/μL platelets, > 11.0 g/dL hemoglobin or 50% improvement for either of these parameters without transfusions or growth factors. CRi was defined as all criteria for CR met but with persistent anemia, thrombocytopenia, neutropenia or a hypocellular bone marrow.

  2. Lymph Node Response Rate [ Time Frame: Up to 45 months ]
    Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lesions.

  3. Overall Survival [ Time Frame: Up to 47 months ]
    Overall survival (OS) was defined as the interval from randomization to death from any cause. Overall survival (months) = (date of death - date of randomization + 1)/30.4375.

  4. Complete Response Rate [ Time Frame: Up to 40 months ]
    Complete response (CR) rate was defined as the percentage of participants who achieved a CR.

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

Key Inclusion Criteria:

  • Previously treated recurrent CLL
  • Measurable lymphadenopathy
  • Requires therapy for CLL
  • Has experienced CLL progression <36 months since the completion of the last prior therapy

Key Exclusion Criteria:

  • Recent history of a major non-CLL malignancy
  • Evidence of an ongoing infection
  • CLL refractory to bendamustine
  • Concurrent participation in another therapeutic clinical trial

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 identifier (NCT number): NCT01569295

  Hide Study Locations
United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States, 35805
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
Stanford Cancer Center
Palo Alto, California, United States, 94035
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
University of Florida
Gainesville, Florida, United States, 32603
United States, Georgia
Winship Cancer Institute at Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Summit Medical Group, P.A.
Morristown, New Jersey, United States, 07962
United States, New York
North Shore University Hospital
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11042
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
Columbia University Medical Center
New York, New York, United States, 10032
United States, Oregon
Willamette Valley Cancer Center
Eugene, Oregon, United States, 97477
United States, South Carolina
Charleston Hematology Oncology
Charleston, South Carolina, United States, 29414
United States, Texas
Texas Oncology
Austin, Texas, United States, 78731
Texas Oncology PA
Dallas, Texas, United States, 75246
Texas Oncology
Fort Worth, Texas, United States, 76104
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Cancer Care Northwest, US Oncology
Spokane, Washington, United States, 99202
Virginia Cancer Specialists, PC
Vancouver, Washington, United States, 98684
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
St Vincent's Hospital - Sydney
Darlinghurst, New South Wales, Australia, 2010
Gosford Hospital
Gosford, New South Wales, Australia, 2250
Australia, Queensland
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Monash Medical Centre - Clayton Campus
Clayton, Victoria, Australia, 3168
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Princess Alexandra Hospital
Woolloongabba, Australia, 4102
Ziekenhuisnetwerk Antwerpen - AZ Stuivenberg
Antwerpen, Belgium, 2060
UZ Gent
Gent, Belgium, 9000
UZ Leuven
Leuven, Belgium, 3000
Canada, Manitoba
Cancer Care Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Clinical Hospital "Dubrava"
Zagreb, Croatia, 10000
Klinichki Bolnicki Centar-Zagreb
Zagreb, Croatia, 10000
University Hospital Merkur
Zagreb, Croatia, 10000
Fakultni nemocnice Brno
Brno, Czechia, 625 00
Fakultní nemocnice Hradec Králové
Hradec Králové, Czechia, 500 05
Fakultni nemocnice Ostrava
Ostrava, Czechia, 708 52
Hopital Henri Mondor
Créteil, France, 94010
Centre Jean Bernard - Clinique Victor Hugo
Le Mans cedex, France, 72015
CHRU Lille-Hôpital Claude Huriez
Lille, France, 59045
Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes
Lyon, France, 69373
Centre Hospitalier de Mulhouse
Mulhouse, France, 68100
CHU Hôtel-Dieu-Service Hématologie
Nantes, France, 44 093
Centre Hospitalier Lyon Sud
Pierre Bénite, France, Pierre Bénite
Hopital Purpan
Toulouse, France, 31059
Hôpitaux de Brabois
Vandoeuvre-lés-Nancy, France, 54511
G. Genimatas Hospital
Athens, Greece, 11527
University General Hospital of Patras
Patras, Greece, 26500
Semmelweis Egyetem
Budapest, Hungary, 1083
Országos Onkológiai Intézet
Budapest, Hungary, 1122
Debreceni Egyetem Orvos- és Egészségtudományi Centrum
Debrecen, Hungary, 4032
Tallian Gyula utca 20-32
Kaposvár, Hungary, 7400
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
Szeged, Hungary, 6720
Mater Misericordiae Hospital
Dublin, Ireland
Spedali Civili di Brescia
Brescia, Italy, 25123
Ospedale Oncologico Regionale A. Businco
Cagliari, Italy, 9121
IRCCS Ospedale San Raffaele
Milano, Italy, 20132
Azienda Ospedaliera Universitaria San Giovanni Battista-Molinette
Torino, Italy, 10126
Szpital Specjalistyczny w Brzozowie
Brzozow, Poland, 36-200
Malopolskie Centrum Medyczne
Krakow, Poland, 30-510
Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi
Lodz, Poland, 93-510
Samodzielny Publiczny Szpital Kliniczny Nr 1
Lublin, Poland, 20-081
Wojewodzki Szpital w Opolu
Opole, Poland, 43-372
Centralny Szpital Kliniczny MSW w Warszawie
Warszawa, Poland, 02-507
Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie
Warszawa, Poland, 02-781
Hospital Santa Maria
Lisboa, Portugal, 1649-035
"Instituto Portugues de Oncologia do Porto Francisco Gentil (IPOPFG, EPE)
Porto, Portugal, 4200-072
Emergency County Clinical Hospital Brasov
Brasov, Romania, 500152
"Colentina" Clinical Hospital
Bucharest, Romania, 20125
"Fundeni" Clinical Institute
Bucharest, Romania, 22328
Regional Oncology Institute Iasi
Iasi, Romania, 700483
Russian Federation
Russian Oncology Research Center (N.N. Blokhin)
Moscow, Russian Federation, 115478
Nizhegorodskaya Regional Clinical Hospital n.a. N.A. Semashko
Nizhniy Novgorod, Russian Federation, 603126
Novosibirsk State Regional Clinical Hospital
Novosibirsk, Russian Federation
Ryazan Regional Clinical Hospital
Ryazan, Russian Federation, 390039
Saratov State Medical University
Saratov, Russian Federation, 410028
Research Institute of Hematology and Blood Transfusion
St. Petersburg, Russian Federation, 193024
State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary #1
Volgograd, Russian Federation, 400138
Hospital Universitario Germans Trias i Pujol
Badalona, Cataluña, Spain, 08916
Hospital Clinic de Barcelona
Barcelona, Cataluña, Spain, 8036
Hospital de la Santa Creu i Sant Pau
Barcelona, Cataluña, Spain, 8041
Hospital 12 de Octubre
Madrid, Madrid, Communidad De, Spain, 28041
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, Communidad De, Spain, 28222
Hospital Universitario de La Princesa
Madrid, Spain, 28033
Gazi University Medical Faculty Gazi Hospital
Ankara, Turkey, 06500
Ankara University Medical Faculty
Ankara, Turkey, 6590
Istanbul University Istanbul Medical Faculty
Istanbul, Turkey, 34093
Ondokuz Mayis University Faculty of Medicine
Samsun, Turkey, 55239
United Kingdom
Birmingham Heartlands Hospital
Birmingham, United Kingdom, B9 5SS
Kent and Canterbury Hospital
Canterbury, United Kingdom, CT1 3NG
University Hospital of Wales
Cardiff, United Kingdom, CF14 4XW
Dorset County Hospital
Dorchester, United Kingdom, DT1 2JY
St. James University Hospital
Leeds, United Kingdom, LS9 7TF
Royal Liverpool University Hospital
Liverpool, United Kingdom, L7 8XP
St Bartholomews Hospital
London, United Kingdom, EC1A 7BE
King's College Hospital
London, United Kingdom, SE5 9RS
Hammersmith Hospital
London, United Kingdom, W12 0NN
University College London
London, United Kingdom, WC1E 6BT
Christie Hospital
Manchester, United Kingdom, M20 4BX
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom, NG5 1PB
Churchill Hospital
Oxford, United Kingdom, OX3 7LE
Royal Cornwall Hospital
Truro, United Kingdom, TR1 3LJ
New Cross Hospital
Wolverhampton, United Kingdom, WV10 0QP
Sponsors and Collaborators
Gilead Sciences
Study Director: Gilead Study Director Gilead Sciences

Zelenetz AD, Robak T, et al. Idelalisib Plus Bendamustine and Rituximab (BR) Is Superior to BR Alone in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results of a Phase 3 Randomized Double-Blind Placebo-Controlled Study. American Society ofHematology (ASH) 57th Annual Meeting & Exposition; 5-8 December 2015; Orlando, FL.
Barrientos JC, Brown JR, et al. Results of a Randomized Double-Blind Placebo-Controlled Phase 3 study Evaluating Idelalisib in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL and Adverse Prognostic Features. American Society of Clinical Oncology (ASCO) 2016 Annual Meeting; 3-7 June 2016; Chicago, IL.
Hillmen, P, Ferra C, et al. Idelalisib in Combination with Bendamustine and Rituximab Improves Overall Survival in Patients with Relapsed/Refractory CLL: Interim Results of a Phase 3 Randomized Double-Blind Placebo-Controlled Study. European Hematology Association (EHA) 21st Annual Meeting; 9-12 June 2016; Copenhagen, Denmark.
Zelenetz AD, Brown JR et al. Updated Analysis of Overall Survival in Randomized Phase III Study of Idelalisib in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL. American Society of Hematology (ASH) 58th Annual Meeting & Exposition; 3-6 December 2016; San Diego, CA

Responsible Party: Gilead Sciences Identifier: NCT01569295     History of Changes
Other Study ID Numbers: GS-US-312-0115
2011-006292-20 ( EudraCT Number )
First Posted: April 3, 2012    Key Record Dates
Results First Posted: February 27, 2018
Last Update Posted: February 27, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:
CAL 101
GS 1101

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors