Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela )

Chronic Lymphocytic Leukemia Clinical Trial

— Tugela  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01569295
• Other study ID #: GS-US-312-0115
• Secondary ID: 2011-006292-20
• Status: Completed
• Phase: Phase 3
• Start date: June 15, 2012
• Est. completion date: June 10, 2019

Study information

• Verified date: March 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the effect of the addition of idelalisib (formerly GS-1101) to bendamustine + rituximab (BR) on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 416
• Est. completion date: June 10, 2019
• Est. primary completion date: June 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Idelalisib
Idelalisib 150 mg administered orally twice daily
• 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
• Bendamustine
Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions
• Placebo to match idelalisib
Placebo to match idelalisib administered orally twice daily

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Medical Centre - Clayton Campus	Clayton	Victoria
Australia	St Vincent's Hospital - Sydney	Darlinghurst	New South Wales
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Princess Alexandra Hospital	Woolloongabba
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Ziekenhuisnetwerk Antwerpen - AZ Stuivenberg	Antwerpen
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Croatia	Clinical Hospital "Dubrava"	Zagreb
Croatia	Klinichki Bolnicki Centar-Zagreb	Zagreb
Croatia	University Hospital Merkur	Zagreb
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultní nemocnice Hradec Králové	Hradec Králové
Czechia	Fakultni nemocnice Ostrava	Ostrava
France	Hopital Henri Mondor	Créteil
France	Centre Jean Bernard - Clinique Victor Hugo	Le Mans cedex
France	CHRU Lille-Hôpital Claude Huriez	Lille
France	Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes	Lyon
France	Centre Hospitalier de Mulhouse	Mulhouse
France	CHU Hôtel-Dieu-Service Hématologie	Nantes
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	Hopital Purpan	Toulouse
France	Hôpitaux de Brabois	Vandoeuvre-lés-Nancy
Greece	G. Genimatas Hospital	Athens
Greece	University General Hospital of Patras	Patras
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Orvos- és Egészségtudományi Centrum	Debrecen
Hungary	Tallian Gyula utca 20-32	Kaposvár
Hungary	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ	Szeged
Ireland	Mater Misericordiae Hospital	Dublin
Italy	Spedali Civili di Brescia	Brescia
Italy	Ospedale Oncologico Regionale A. Businco	Cagliari
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria San Giovanni Battista-Molinette	Torino
Poland	Szpital Specjalistyczny w Brzozowie	Brzozow
Poland	Malopolskie Centrum Medyczne	Krakow
Poland	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi	Lodz
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1	Lublin
Poland	Wojewodzki Szpital w Opolu	Opole
Poland	Centralny Szpital Kliniczny MSW w Warszawie	Warszawa
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie	Warszawa
Portugal	Hospital Santa Maria	Lisboa
Portugal	"Instituto Portugues de Oncologia do Porto Francisco Gentil (IPOPFG, EPE)	Porto
Romania	Emergency County Clinical Hospital Brasov	Brasov
Romania	"Colentina" Clinical Hospital	Bucharest
Romania	"Fundeni" Clinical Institute	Bucharest
Romania	Regional Oncology Institute Iasi	Iasi
Russian Federation	Russian Oncology Research Center (N.N. Blokhin)	Moscow
Russian Federation	Nizhegorodskaya Regional Clinical Hospital n.a. N.A. Semashko	Nizhniy Novgorod
Russian Federation	Novosibirsk State Regional Clinical Hospital	Novosibirsk
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
Russian Federation	Saratov State Medical University	Saratov
Russian Federation	Research Institute of Hematology and Blood Transfusion	St. Petersburg
Russian Federation	State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary #1	Volgograd
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Cataluña
Spain	Hospital Clinic de Barcelona	Barcelona	Cataluña
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña
Spain	Hospital 12 de Octubre	Madrid	Madrid, Communidad De
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid, Communidad De
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Gazi University Medical Faculty Gazi Hospital	Ankara
Turkey	Istanbul University Istanbul Medical Faculty	Istanbul
Turkey	Ondokuz Mayis University Faculty of Medicine	Samsun
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Kent and Canterbury Hospital	Canterbury
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Dorset County Hospital	Dorchester
United Kingdom	St. James University Hospital	Leeds
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	Hammersmith Hospital	London
United Kingdom	King's College Hospital	London
United Kingdom	St Bartholomews Hospital	London
United Kingdom	University College London	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal Cornwall Hospital	Truro
United Kingdom	New Cross Hospital	Wolverhampton
United States	Winship Cancer Institute at Emory University	Atlanta	Georgia
United States	Texas Oncology	Austin	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Charleston Hematology Oncology	Charleston	South Carolina
United States	Texas Oncology PA	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Texas Oncology	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	UCLA Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Summit Medical Group, P.A.	Morristown	New Jersey
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Stanford Cancer Center	Palo Alto	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Cancer Care Northwest, US Oncology	Spokane	Washington
United States	Virginia Cancer Specialists, PC	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Croatia,  Czechia,  France,  Greece,  Hungary,  Ireland,  Italy,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

References & Publications (5)

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, Barrientos JC, Brown JR, Coiffier B, Delgado J, Egyed M, Ghia P, Illés Á, Jurczak W, Marlton P, Montillo M, Morschhauser F, Pristupa AS, Robak T, Sharman JP, Simpson D, Smolej L, Tausch E, Adewoye AH, Dreiling LK, Kim Y, Stilgenbauer S, Hillmen P. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017 Mar;18(3):297-311. doi: 10.1016/S1470-2045(16)30671-4. Epub 2017 Jan 28. — View Citation

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

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	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.	Up to 84 months
Secondary	Overall Response Rate (ORR)	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.	Up to 84 months
Secondary	Lymph Node Response Rate	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.	Up to 84 months
Secondary	Overall Survival	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.	Up to 84 months
Secondary	Complete Response Rate	Complete response (CR) rate was defined as the percentage of participants who achieved a CR.	Up to 84 months