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)
- Conditions
- Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma
- Interventions
- Registration Number
- NCT04965493
- Lead Sponsor
- Loxo Oncology, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 600
- 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)
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (PVR) Pirtobrutinib Fixed duration pirtobrutinib in combination with venetoclax and rituximab Arm A (PVR) Venetoclax Fixed duration pirtobrutinib in combination with venetoclax and rituximab Arm A (PVR) Rituximab Fixed duration pirtobrutinib in combination with venetoclax and rituximab Arm B (VR) Venetoclax Venetoclax with rituximab Arm B (VR) Rituximab Venetoclax with rituximab
- Primary Outcome Measures
Name Time Method To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B) Up to approximately 5 years Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018
- Secondary Outcome Measures
Name Time Method To evaluate the efficacy of Arm A compared to Arm B: Progression-free survival (PFS) Up to approximately 5 years Assessments of efficacy include PFS, assessed by investigator
To evaluate the efficacy of Arm A compared to Arm B: Overall survival (OS) Up to approximately 5 years Assessments of efficacy include OS
To evaluate the efficacy of Arm A compared to Arm B: Time to next treatment (TTNT) Up to approximately 5 years Assessments of efficacy include TTNT
To evaluate the efficacy of Arm A compared to Arm B: Event-free survival (EFS) Up to approximately 5 years Assessments of efficacy include EFS
To evaluate the efficacy of Arm A compared to Arm B: Overall response rate (ORR) Up to approximately 5 years Assessments of efficacy include ORR
To evaluate the efficacy of Arm A compared to Arm B in patient-reported disease-related symptoms Up to approximately 5 years Based on time to worsening of CLL/SLL-related symptoms
To evaluate the efficacy of Arm A compared to Arm B in patient-reported physical functioning Up to approximately 5 years Based on time to worsening of physical functioning
Trial Locations
- Locations (177)
IRCCS - AOU di Bologna
🇮🇹Bologna, Italy
Ospedale Santa Croce e Carle
🇮🇹Cuneo, Italy
A.O.U. di Modena
🇮🇹Modena, Italy
Policlinico Umberto I - Haematology
🇮🇹Rome, Italy
Hopital Saint Eloi
🇫🇷Montpellier Cedex, France
Hopital de la Pitie Salpetriere
🇫🇷Paris CEDEX 13, France
Hopital Saint Louis
🇫🇷Paris, France
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Ironwood Physicians, Ironwood Cancer and Research Centers
🇺🇸Chandler, Arizona, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Scripps Mercy Hospital
🇺🇸San Diego, California, United States
Providence Medical Foundation
🇺🇸Santa Rosa, California, United States
Stamford Hospital
🇺🇸Stamford, Connecticut, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
Cancer Specialists of North Florida -St Augustine
🇺🇸Saint Augustine, Florida, United States
Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
Mission Cancer and Blood
🇺🇸Des Moines, Iowa, United States
Pikeville Medical Center, Inc.
🇺🇸Pikeville, Kentucky, United States
American Oncology Partners of Maryland, PA
🇺🇸Bethesda, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
The Mount Sinai Hospital
🇺🇸New York, 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
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Novant Cancer Institute Charlotte
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Regional Medical Oncology Center
🇺🇸Wilson, North Carolina, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
The James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Oncology Associates of Bridgeport P.C.
🇺🇸Eugene, Oregon, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute SCRI
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology PLLC
🇺🇸Nashville, Tennessee, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
USO - Texas Oncology - San Antonio
🇺🇸San Antonio, Texas, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Virginia Cancer Specialists, PC - Lee Highway
🇺🇸Fairfax, Virginia, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Swedish Cancer Institute; STE 1020
🇺🇸Seattle, Washington, United States
Northwest Cancer Specialists PC
🇺🇸Vancouver, Washington, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Peninsula Private Hospital
🇦🇺Frankston, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
St Vincent's Hospital
🇦🇺Melbourne, Victoria, Australia
Sir Charles Gairdner Hospital
🇦🇺Perth, Western Australia, Australia
Groupe Jolimont
🇧🇪La Louvière, Hainaut, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
CHU UCL Namur site Godinne
🇧🇪Yvoir, Belgium
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
BC Cancer Vancouver
🇨🇦Vancouver, British Columbia, Canada
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Fujian Provincial Cancer Hospial
🇨🇳Fuzhou, Fujian, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Zhongshan City People's Hospital
🇨🇳Zhongshan, Guangdong, China
Guangxi Medical University Affiliated Tumor Hospital
🇨🇳Nanning, Guangxi, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Wu Han Tongji Hospital
🇨🇳Wu Han, Hu Bei, China
Wuhan Union Hospital
🇨🇳Wuhan, Hubei, China
Yichang Central People's Hospital
🇨🇳Yichang, Hubei, China
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital Of University Of South China
🇨🇳Hengyang, Hunan, China
The Affiliated Hospital of Inner Mongolia Medical University
🇨🇳Hohhot, Inner Mongolia, China
Nantong Tumor Hospital
🇨🇳Nantong, Jiangsu, China
Wuxi People's Hospital
🇨🇳Wuxi, Jiangsu, China
Jiangxi Provincial Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Jiangsu Province Hospital
🇨🇳Nanjing, Nanjing, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao City, Shandong, China
Shanghai Jiaotong University School of Medicine Ruijin Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Tongren Hospital
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Peking University People's Hospital
🇨🇳Beijing, Xicheng District, China
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
The First People's Hospital of Yunnan Province
🇨🇳Kunming, Yunnan, China
First Affiliated Hosp of College of Med, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Chongqing Cancer Hospital
🇨🇳Chongqing, China
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Hradec Králové, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Rigshospitalet
🇩🇰Copenhagen, Denmark
CHU de Nantes - Hotel Dieu
🇫🇷Nantes, Cedex 1, France
Hôpital de Pontchaillou
🇫🇷Rennes, Cedex 9, France
Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen
🇫🇷Rouen, Seine-Maritime, France
Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois
🇫🇷Morvan, Vandoeuvre Les Nancy, France
Centre Hospitalier du Mans
🇫🇷Le Mans, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite Cedex, France
Pole Regionalde Cancérologie(CHU de Poitiers)
🇫🇷Politiers, France
ICANS_Institut de Cancerologie Strasbourg Europe
🇫🇷Strasbourg, France
CHRU De Tours
🇫🇷Tours Cedex, France
Uniklinik Köln
🇩🇪Kerpener, Köln, Germany
München Klinik Schwabing
🇩🇪Koelner Platz 1, München, Germany
Klinikum Chemnitz GmbH
🇩🇪Chemnitz, Sachsen, Germany
Universitätsklinikum Leipzig AöR Klinik und Poliklinik für Hämatologie
🇩🇪Leipzig, Saxony, Germany
Charité - Hämatologie - Onkologie - Tumorimmunologie, CC14 - Campus Benjamin Franklin
🇩🇪Berlin, Germany
Universtitätsklinikum Essen AöR
🇩🇪Essen, Germany
Unimedizin RostockZIM III -Haemtologie
🇩🇪Rostock, Germany
Gemeinschaftspraxis Dres. Schöttker & Pretscher, z.Hd. Sophie Enz
🇩🇪Würzburg, Germany
National Institute of Oncology
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Mater Misericordiae Hospital
🇮🇪Dublin 7, Ireland
University Hospital Waterford
🇮🇪Waterford, Ireland
Rabin Medical Center
🇮🇱Petah Tikva, HaMerkaz, Israel
Kaplan Medical Center
🇮🇱Rehovot, HaMerkaz, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Pugliese Ciaccio
🇮🇹Catanzaro, Italy
ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C
🇮🇹Milan, Milano, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Emilia-Romagna, Italy
AOU Arcispedale Sant'Anna
🇮🇹Cona, Italy
A.O.U. Citta' della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Florence, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedale Maggiore Della Carita
🇮🇹Novara, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Kochi Medical School Hospital
🇯🇵Nankoku, Kochi, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Japanese Foundation for Cancer Research
🇯🇵Koto, Tokyo, Japan
University of Yamanashi Hospital
🇯🇵Chuo, Yamanshi, Japan
Tokyo Medical and Dental University Hospital
🇯🇵Bunkyo-ku, Japan
National Cancer Center Hospital East
🇯🇵Chiba-Ken, Japan
University of Fukui Hospital
🇯🇵Fukui, Japan
Kyoto Furitsu Medical University Hospital
🇯🇵Kyoto, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Osaka City General Hospital
🇯🇵Osaka, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Akershus Universitetssykehus
🇳🇴Nordbyhagen, Norway
St-Olavs Hospital
🇳🇴Trondheim, Norway
Szpitale Pomorskie Sp. z o. o.
🇵🇱Gdynia, Pomorskie, Poland
MICS Centrum Medyczne Torun
🇵🇱Torun, Pomorskie, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Pratia MCM Krakow
🇵🇱Krakow, Poland
Klinika Hematoonkologii i Transplantacji Szpiku,Samodzielny Publiczny Szpital Kliniczny Nr 1
🇵🇱Lublin, Poland
Instytut Hermatologii I Transfuzjologii
🇵🇱Warszawa, Poland
Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii
🇵🇱Łódź, Poland
Singapore General Hospital
🇸🇬Singapore, Singapore
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Hospital Puerta De Hierro
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Costa Del Sol
🇪🇸Marbella, Malaga, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario de Toledo
🇪🇸Toledo, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Skanes Universitetssjukhus, Hematoloaimottagningen
🇸🇪Lund, Sweden
Karolinska Universitetssjukhuset i Solna
🇸🇪Stockholm, Sweden
Ospedale Regionale Bellinzona e Valli
🇨🇭Bellinzona, Ticino, Switzerland
Luzerner Kantonsspital
🇨🇭Luzern, Switzerland
Birmingham Heartlands Hospital
🇬🇧Birmingham, England, United Kingdom
Royal Marsden Hospital
🇬🇧London, United Kingdom
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
St James's University Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom