Clinical trial NCT05023980: A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: BTKi
BTK Inhibitor
Hematologic Disease
Lymphoma, non-Hodgkin's
Lymphoma, B-cell
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2021-08-27
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients will be randomized 1:1 into Arm A and Arm B. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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 10⁹/liter (L) (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/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

Primary outcomes:
measure: To evaluate progression-free survival (PFS) of pirtobrutinib (Arm A) compared to bendamustine and rituximab (Arm B)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: To evaluate the effectiveness of Arm A compared to Arm B: Progression-free survival (PFS)
timeFrame: Up to approximately 5 years
measure: To evaluate the effectiveness of Arm A compared to Arm B: Overall survival (OS)
timeFrame: Up to approximately 5 years
measure: To evaluate the effectiveness of Arm A compared to Arm B: Time to next treatment (TTNT)
timeFrame: Up to approximately 5 years
measure: To evaluate the effectiveness of Arm A compared to Arm B: Overall response rate (ORR)
timeFrame: Up to approximately 5 years
measure: To evaluate the effectiveness of Arm A compared to Arm B: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms
timeFrame: Up to approximately 5 years
measure: To evaluate the effectiveness of Arm A compared to Arm B in patient-reported physical functioning
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Coral Springs
country: United States
facility: Oncology-Hematology Associates of West Broward
state: Florida
city: Brick
country: United States
facility: New Jersey Center for Cancer Research
state: New Jersey
city: Westbury
country: United States
facility: Clinical Research Alliance, Inc.
state: New York
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Wentworthville
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg
city: Vienna
country: Austria
facility: Klinik Ottakring
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado - Mae de Deus Center
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Hemocentro Unicamp
state: São Paulo
city: Jaú
country: Brazil
facility: Fundação Doutor Amaral Carvalho
state: São Paulo
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi" EAD
city: Sofia
country: Bulgaria
facility: UMHAT 'Sv. Ivan Rilski', EAD
city: Sofia
country: Bulgaria
facility: "SHATHD" EAD, Sofia
city: Stara Zagora
country: Bulgaria
facility: UMHAT - Prof. Dr. Stoyan Kirkovich" AD
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyany
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Nanjing
city: Changning District
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of hematology&blood disease hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First People's Hospital of Hangzhou Linping District
state: Zhejiang
city: Beijing
country: China
facility: Beijing Hospital
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Le Mans
country: France
facility: Hospitalier Le Mans
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos-es Egészsegtudomanyi Centrum
city: Nyíregyháza
country: Hungary
facility: SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
city: Székesfehérvár
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Rionero In Vulture
country: Italy
facility: Irccs Crob
state: Potenza
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
city: Novara
country: Italy
facility: Azienda Ospedale Maggiore Della Carita
city: Perugia
country: Italy
facility: Istituto di Ematologia-C.R.E.O. (Centro di Ricerche Emato-Oncologich)
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria Terni
city: Trieste
country: Italy
facility: Azienda sanitaria integrata università di Trieste
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Chiba-Shi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Yoshida-Gun
country: Japan
facility: Fukui Medical University Hospital
state: Fukui
city: Sapporo-shi
country: Japan
facility: Hokuyukai Sapporo Hokuyu Hospital
state: Hokkaido
city: Nankoku
country: Japan
facility: Kochi Medical School Hospital
state: Kochi
city: Sendai-shi
country: Japan
facility: NHO Sendai Medical Center
state: Miyagi-Ken
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Koshigaya
country: Japan
facility: Dokkyo Medical University - Koshigaya Hospital
state: Saitama
city: Chuo
country: Japan
facility: University of Yamanashi Hospital
state: Yamanshi
city: Aomori
country: Japan
facility: Aomori Prefectural Centeral Hospital
city: Fukoka-ken
country: Japan
facility: JCHO Kyushu Hospital
city: Namdong-gu
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Incheon-gwangyeoksi [Incheon]
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul, Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul-teukbyeolsi [Seoul]
city: Seocho-Gu
country: Korea, Republic of
facility: The Catholic University of Korea-Seoul St. Mary's Hospital
state: Seoul
city: Busan
country: Korea, Republic of
facility: Inje Univ Busan Paik Hospital
city: Takapuna
country: New Zealand
facility: North Shore Hospital, Haematology Research
state: Auckland
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
state: Bay Of Plenty
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Papatoetoe
country: New Zealand
facility: Middlemore Clinical Trials
city: Iwaszkiewicza 5
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
state: Legnica
city: Lublin
country: Poland
facility: Klinika Hematoonkologii i Transplantacji Szpiku SPSK1 Lublin
state: Lubelskie V
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
state: Poznan
city: Biała Podlaska
country: Poland
facility: KO-MED Centra Kliniczne
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. Antoniego Jurasza
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Kraków
country: Poland
facility: Pratia MCM Krakow
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej
city: Toruń
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Cuire - Państwowy Instytut Badawczy
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny Klinika
city: Braga
country: Portugal
facility: Centro Clínico Académico - Braga (2CA-Braga) (Hospital de Braga)
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil, EPE
city: Craiova
country: Romania
facility: Spitalul Clinic Municipal Filantropia Craiova
state: Dolj
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni - Centrul de Hematologie si Transplant Medular
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
city: Iasi
country: Romania
facility: Institutului Regional de Oncologie IASI
city: St-Petersburg
country: Russian Federation
facility: Academician I.P. Pavlov First St-Petersburg State Medical University
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Changhua
country: Taiwan
facility: Chang Bing Show Chwan Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: