Clinical trial NCT04965493: A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Official title: A Phase 3 Open-Label, Randomized Study of Fixed Duration Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab Versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-322)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: BTKi
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: 2021-07-16
Enrollment: 600
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.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy and safety of fixed duration pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with CLL/SLL who have been previously treated with at least one prior line of therapy. Participation could last up to five years.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
* Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor
* Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL) and absolute neutrophil count ≥1.0 x 10⁹/L
* Adequate organ function
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion Criteria:

* Known or suspected Richter's transformation at any time preceding enrollment
* Prior therapy with a non-covalent (reversible) BTK inhibitor
* Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
* Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers
* Prior therapy with venetoclax
* Central nervous system (CNS) involvement
* Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
* Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
* Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days
* Active hepatitis B or hepatitis C
* Known active cytomegalovirus (CMV) infection
* Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA)
* Significant cardiovascular disease
* Vaccination with a live vaccine within 28 days prior to randomization
* Patients with the following hypersensitivity:

  * Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax
  * Prior significant hypersensitivity to rituximab
  * Known allergy to allopurinol and inability to take uric acid lowering agent

Primary outcomes:
measure: To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: To evaluate the efficacy of Arm A compared to Arm B: Progression-free survival (PFS)
timeFrame: Up to approximately 5 years
measure: To evaluate the efficacy of Arm A compared to Arm B: Overall survival (OS)
timeFrame: Up to approximately 5 years
measure: To evaluate the efficacy of Arm A compared to Arm B: Time to next treatment (TTNT)
timeFrame: Up to approximately 5 years
measure: To evaluate the efficacy of Arm A compared to Arm B: Event-free survival (EFS)
timeFrame: Up to approximately 5 years
measure: To evaluate the efficacy of Arm A compared to Arm B: Overall response rate (ORR)
timeFrame: Up to approximately 5 years
measure: To evaluate the efficacy of Arm A compared to Arm B in patient-reported disease-related symptoms
timeFrame: Up to approximately 5 years
measure: To evaluate the efficacy of Arm A compared to Arm B in patient-reported physical functioning
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Physicians, Ironwood Cancer and Research Centers
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Scripps Mercy Hospital
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation
state: California
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Augustine
country: United States
facility: Cancer Specialists of North Florida -St Augustine
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists East
state: Florida
city: Des Moines
country: United States
facility: Mission Cancer and Blood
state: Iowa
city: Pikeville
country: United States
facility: Pikeville Medical Center, Inc.
state: Kentucky
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Cancer Institute Charlotte
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Wilson
country: United States
facility: Regional Medical Oncology Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Bridgeport P.C.
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute SCRI
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: USO - Texas Oncology - San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC - Lee Highway
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute; STE 1020
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists PC
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: La Louvière
country: Belgium
facility: Groupe Jolimont
state: Hainaut
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Yvoir
country: Belgium
facility: CHU UCL Namur site Godinne
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospial
state: Fujian
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan City People's Hospital
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
state: Guangxi
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wu Han
country: China
facility: Wu Han Tongji Hospital
state: Hu Bei
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Yichang
country: China
facility: Yichang Central People's Hospital
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital Of University Of South China
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial Cancer Hospital
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Nanjing
city: Qingdao City
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine Ruijin Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Beijing
country: China
facility: Peking University People's Hospital
state: Xicheng District
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: First Affiliated Hosp of College of Med, Zhejiang University
state: Zhejiang
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
state: Hradec Králové
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
state: Cedex 1
city: Rennes
country: France
facility: Hôpital de Pontchaillou
state: Cedex 9
city: Rouen
country: France
facility: Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen
state: Seine-Maritime
city: Morvan
country: France
facility: Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois
state: Vandoeuvre Les Nancy
city: Le Mans
country: France
facility: Centre Hospitalier du Mans
city: Montpellier Cedex
country: France
facility: Hopital Saint Eloi
city: Paris CEDEX 13
country: France
facility: Hopital de la Pitie Salpetriere
city: Paris
country: France
facility: Hopital Saint Louis
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Politiers
country: France
facility: Pole Regionalde Cancérologie(CHU de Poitiers)
city: Strasbourg
country: France
facility: ICANS_Institut de Cancerologie Strasbourg Europe
city: Tours Cedex
country: France
facility: CHRU De Tours
city: Kerpener
country: Germany
facility: Uniklinik Köln
state: Köln
city: Koelner Platz 1
country: Germany
facility: München Klinik Schwabing
state: München
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz GmbH
state: Sachsen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR Klinik und Poliklinik für Hämatologie
state: Saxony
city: Berlin
country: Germany
facility: Charité - Hämatologie - Onkologie - Tumorimmunologie, CC14 - Campus Benjamin Franklin
city: Essen
country: Germany
facility: Universtitätsklinikum Essen AöR
city: Rostock
country: Germany
facility: Unimedizin RostockZIM III -Haemtologie
city: Würzburg
country: Germany
facility: Gemeinschaftspraxis Dres. Schöttker & Pretscher, z.Hd. Sophie Enz
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Dublin 7
country: Ireland
facility: Mater Misericordiae Hospital
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
state: HaMerkaz
city: Rehovot
country: Israel
facility: Kaplan Medical Center
state: HaMerkaz
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Emilia-Romagna
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Florence
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C
state: Milano
city: Bologna
country: Italy
facility: IRCCS - AOU di Bologna
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Pugliese Ciaccio
city: Cona
country: Italy
facility: AOU Arcispedale Sant'Anna
city: Cuneo
country: Italy
facility: Ospedale Santa Croce e Carle
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Modena
country: Italy
facility: A.O.U. di Modena
city: Novara
country: Italy
facility: Azienda Ospedale Maggiore Della Carita
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
city: Rome
country: Italy
facility: Policlinico Umberto I - Haematology
city: Torino
country: Italy
facility: A.O.U. Citta' della Salute e della Scienza di Torino
city: Nankoku
country: Japan
facility: Kochi Medical School Hospital
state: Kochi
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto
country: Japan
facility: Japanese Foundation for Cancer Research
state: Tokyo
city: Chuo
country: Japan
facility: University of Yamanashi Hospital
state: Yamanshi
city: Bunkyo-ku
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Chiba-Ken
country: Japan
facility: National Cancer Center Hospital East
city: Fukui
country: Japan
facility: University of Fukui Hospital
city: Kyoto
country: Japan
facility: Kyoto Furitsu Medical University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Korea
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Nordbyhagen
country: Norway
facility: Akershus Universitetssykehus
city: Trondheim
country: Norway
facility: St-Olavs Hospital
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o. o.
state: Pomorskie
city: Torun
country: Poland
facility: MICS Centrum Medyczne Torun
state: Pomorskie
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Lublin
country: Poland
facility: Klinika Hematoonkologii i Transplantacji Szpiku,Samodzielny Publiczny Szpital Kliniczny Nr 1
city: Warszawa
country: Poland
facility: Instytut Hermatologii I Transfuzjologii
city: Łódź
country: Poland
facility: Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Barcelona [Barcelona]
city: Majadahonda
country: Spain
facility: Hospital Puerta De Hierro
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Marbella
country: Spain
facility: Hospital Costa Del Sol
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Toledo
country: Spain
facility: Hospital Universitario de Toledo
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus, Hematoloaimottagningen
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset i Solna
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli
state: Ticino
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Leeds
country: United Kingdom
facility: St James's University Hospital
state: West Yorkshire
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
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: