A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Chronic Lymphocytic Leukemia Clinical Trial

— BRUIN CLL-313  

Official title:

A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05023980
• Other study ID #: LOXO-BTK-20023
• Secondary ID: J2N-OX-JZNP
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 23, 2021
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: May 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of CLL/SLL requiring therapy, per iwCLL 2018 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Adequate organ function
• Platelets greater than or equal to (=)75 x 10?/liter (L) (=50 × 10?/L for patients with evidence of bone marrow infiltrate), hemoglobin =8 grams/deciliter (g/dL), and absolute neutrophil count =0.75 x 10?/L
• Kidney function: Estimated creatinine clearance =40 milliliters per minute (mL/min)

Exclusion Criteria:

• Known or suspected Richter's transformation at any time preceding enrollment
• Prior systemic therapy for CLL/SLL
• Presence of 17p deletion
• Central nervous system (CNS) involvement
• Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
• Significant cardiovascular disease
• Active hepatitis B or hepatitis C
• Active cytomegalovirus (CMV) infection
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
• Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
• Concurrent use of investigational agent or anticancer therapy except hormonal therapy
• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
• Vaccination with a live vaccine within 28 days prior to randomization
• Patients with the following hypersensitivity:
• Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or bendamustine
• Prior significant hypersensitivity to rituximab

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pirtobrutinib
Oral
• Bendamustine
IV
• Rituximab
IV

Locations

Country	Name	City	State
Australia	Peninsula Private Hospital	Frankston	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Westmead Hospital	Wentworthville	New South Wales
Austria	Uniklinikum Salzburg	Salzburg
Austria	Klinik Ottakring	Vienna
Brazil	Hemocentro Unicamp	Campinas	São Paulo
Brazil	Centro Integrado de Oncologia de Curitiba	Curitiba	Paraná
Brazil	Fundação Doutor Amaral Carvalho	Jaú	São Paulo
Brazil	Instituto do Câncer - Hospital São Vicente de Paulo	Passo Fundo	Rio Grande Do Sul
Brazil	Centro Gaucho Integrado - Mae de Deus Center	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Bulgaria	UMHAT "Sveti Georgi" EAD	Plovdiv
Bulgaria	"SHATHD" EAD, Sofia	Sofia
Bulgaria	UMHAT 'Sv. Ivan Rilski', EAD	Sofia
Bulgaria	UMHAT - Prof. Dr. Stoyan Kirkovich" AD	Stara Zagora
China	Beijing Hospital	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Shanghai Tongren Hospital	Changning District	Shanghai
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Hainan General Hospital	Haikou
China	The First People's Hospital of Hangzhou Linping District	Hangzhou	Zhejiang
China	Anhui Provincial Cancer Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Nanjing
China	Shengjing Hospital of China Medical University	Shenyany	Liaoning
China	Institute of hematology&blood disease hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	CHD Vendee	La Roche-sur-Yon	Vendee
France	Hospitalier Le Mans	Le Mans
France	Chu Nimes/Institut De Cancerologie Du Gard	Nimes
France	CHRU De Tours	Tours	Tours Cedex 9
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	National Institute of Oncology	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Orvos-es Egészsegtudomanyi Centrum	Debrecen
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyíregyháza
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár
Ireland	Mater Misericordiae Hospital	Dublin 7
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII	Bergamo
Italy	IRCCS - AOU di Bologna	Bologna	BO
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C	Milano
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)	Monza
Italy	Azienda Ospedale Maggiore Della Carita	Novara
Italy	Azienda Ospedaliera Vincenzo Cervello	Palermo
Italy	Istituto di Ematologia-C.R.E.O. (Centro di Ricerche Emato-Oncologich)	Perugia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	PI
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	Irccs Crob	Rionero In Vulture	Potenza
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Azienda Ospedaliera Santa Maria Terni	Terni
Italy	A.O.U. Citta' della Salute e della Scienza di Torino	Torino
Italy	Azienda Ospedaliera Card. G. Panico	Tricase (Le)
Italy	Azienda sanitaria integrata università di Trieste	Trieste
Japan	Chiba Cancer Center	Chiba-Shi	Chiba
Japan	University of Yamanashi Hospital	Chuo	Yamanshi
Japan	JCHO Kyushu Hospital	Fukoka-ken
Japan	NHO Mito Medical Center	Ibaraki-machi	HigaShiibaraki-Gun
Japan	Kagoshima University Hospital	Kagoshima
Japan	Saitama Medical Center	Kawagoe	Saitama
Japan	Hospital of University of Occupational and Environmental Health	Kitakyushu-shi	Fukuoka
Japan	Dokkyo Medical University - Koshigaya Hospital	Koshigaya	Saitama
Japan	Our Lady of the Snow St. Mary's Hospital	Kurume-shi	Fukuoka-Ken
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Nagoya Medical Center	Nagoya	Aichi
Japan	Kochi Medical School Hospital	Nankoku	Kochi
Japan	Okayama University Hospital	Okayama
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tohoku University Hospital	Sendai-shi	Miyagi
Japan	Kanagawa cancer center	Yokohama	Kanagawa
Japan	Fukui Medical University Hospital	Yoshida-Gun	Fukui
Korea, Republic of	Inje Univ Busan Paik Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Namdong-gu	Incheon-gwangyeoksi [Incheon]
Korea, Republic of	The Catholic University of Korea-Seoul St. Mary's Hospital	Seocho-Gu	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul, Korea
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [Seoul]
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Middlemore Clinical Trials	Papatoetoe
New Zealand	North Shore Hospital, Haematology Research	Takapuna	Auckland
New Zealand	Tauranga Hospital	Tauranga	Bay Of Plenty
Poland	KO-MED Centra Kliniczne	Biala Podlaska
Poland	Szpital Uniwersytecki nr 2 im. dr Jana Biziela w BydgoszczyKlinika Hematologii	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Wojewodzki Szpital Specjalistyczny	Iwaszkiewicza 5	Legnica
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia MCM Krakow	Kraków
Poland	Centrum Onkologii Ziemi Lubelskiej	Lublin
Poland	Klinika Hematoonkologii i Transplantacji Szpiku SPSK1 Lublin	Lublin	Lubelskie V
Poland	Szpital Wojewodzki w Opolu	Opole
Poland	Centrum Medyczne Pratia Poznan	Skorzewo	Poznan
Poland	Nasz Lekarz Osrodek Badan Klinicznych	Torun
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Cuire - Panstwowy Instytut Badawczy	Warsaw
Poland	Uniwersytecki Szpital Kliniczny Klinika	Wroclaw
Portugal	Centro Clínico Académico - Braga (2CA-Braga) (Hospital de Braga)	Braga
Portugal	Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria	Lisboa
Portugal	Hospital de Sao Joao E.P.E.	Porto
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil, EPE	Porto
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova De Gaia
Romania	Institutul Clinic Fundeni - Centrul de Hematologie si Transplant Medular	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Romania	Spitalul Clinic Coltea	Bucuresti
Romania	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic Municipal Filantropia Craiova	Craiova	Dolj
Romania	Institutului Regional de Oncologie IASI	Iasi
Romania	Spitalul Clinic Judetean De Urgenta Oradea	Oradea
Romania	Spitalul Clinic Judetean de Urgenta Targu Mures	Targu Mures
Russian Federation	Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"	Omsk	Omskaya Oblast
Russian Federation	Regional Oncology Dispensary	Penza
Russian Federation	Academician I.P. Pavlov First St-Petersburg State Medical University	St-Petersburg
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Duran I Reynals	L'Hospitalet De Llobregat
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Taiwan	Chang Bing Show Chwan Memorial Hospital	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan City
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	New Cross Hospital	Wolverhampton
United States	New Jersey Center for Cancer Research	Brick	New Jersey
United States	Ascension St. John Hospital	Grosse Pointe Woods	Michigan
United States	Central Maine Medical Center	Lewiston	Maine
United States	California Research Institute	Los Angeles	California
United States	Oncology-Hematology Associates of West Broward	Tamarac	Florida
United States	Clinical Research Alliance, Inc.	Westbury	New York
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Loxo Oncology, Inc.	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Bulgaria,  China,  Czechia,  France,  Hungary,  Ireland,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate progression-free survival (PFS) of pirtobrutinib (Arm A) compared to bendamustine and rituximab (Arm B)	Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Response Criteria	Up to approximately 5 years
Secondary	To evaluate the effectiveness of Arm A compared to Arm B: Progression-free survival (PFS)	Assessments of effectiveness include PFS, assessed by investigator	Up to approximately 5 years
Secondary	To evaluate the effectiveness of Arm A compared to Arm B: Overall survival (OS)	Assessments of effectiveness include OS, assessed by investigator	Up to approximately 5 years
Secondary	To evaluate the effectiveness of Arm A compared to Arm B: Time to next treatment (TTNT)	Assessments of effectiveness include TTNT, assessed by investigator	Up to approximately 5 years
Secondary	To evaluate the effectiveness of Arm A compared to Arm B: Overall response rate (ORR)	Assessments of effectiveness include ORR, assessed by investigator and IRC	Up to approximately 5 years
Secondary	To evaluate the effectiveness of Arm A compared to Arm B: Duration of Response (DOR)	Assessments of effectiveness include DOR, assessed by investigator and IRC	Up to approximately 5 years
Secondary	To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms	Based on time to worsening of CLL/SLL-related symptoms	Up to approximately 5 years
Secondary	To evaluate the effectiveness of Arm A compared to Arm B in patient-reported physical functioning	Based on time to worsening of physical functioning	Up to approximately 5 years

External Links

•   A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN CLL-313)