A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
- Conditions
- Chronic Lymphocytic LeukemiaLeukemia, B-cellLeukemia, LymphocyticSmall Lymphocytic Lymphoma
- Interventions
- Registration Number
- NCT05254743
- Lead Sponsor
- Loxo Oncology, Inc.
- Brief Summary
The purpose of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL. Participants may or may not have already had treatment for their cancer. Participation could last up to six years.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 650
-
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 ≥ 50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis,
- Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
- Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis
- Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)
- Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment
- Known or suspected central nervous system (CNS) involvement
- A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease
- Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
- Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter
- Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
- Active cytomegalovirus (CMV) infection
- Active uncontrolled systemic bacterial, viral, or fungal infection
- Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
- Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments
- Ongoing inflammatory bowel disease
- Prior exposure to BTK inhibitor (covalent or noncovalent)
- Concurrent use of investigational agent or anticancer therapy except hormonal therapy
- Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
- Use of > 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug
- Vaccination with a live vaccine within 28 days prior to randomization
- Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment
- Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ibrutinib Ibrutinib Administered orally. Pirtobrutinib Pirtobrutinib Administered orally.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Baseline to best overall response at or before the initiation of subsequent anti-cancer therapy (if any) (approximately 3 years and 5 months) ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months) PFS by IRC per iwCLL 2018 criteria
Duration of Response (DOR) Time from the date of the first documented response of CR, CRi, nPR or PR to the earlier of documentation of definitive PD (per iwCLL 2018 criteria) or death from any cause (approximately 2 years) DOR
Time to Next Treatment (TTNT) Randomization to initiation of the next systemic anticancer therapy for CLL/SLL or death from any cause, whichever occurs first (approximately 6 years) TTNT
Time to Worsening (TTW) of CLL/SLL Related Symptoms Randomization to time to worsening symptoms (approximately 6 years) Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.
Event-Free Survival (EFS) Randomization to first occurrence of treatment discontinuation due to adverse event/toxicity, treatment-emergent atrial fibrillation or atrial flutter of any grade, progressive disease (PD) or death (approximately 4 years) EFS by IRC per iwCLL 2018 criteria
Overall Survival (OS) Randomization to death from any cause (approximately 6 years) OS
Trial Locations
- Locations (176)
Eisenhower Army Medical Center
🇺🇸Rancho Mirage, California, United States
Alta Bates Summit Medical Center
🇺🇸Berkeley, California, United States
Baylor Scott & White Health
🇺🇸Round Rock, Texas, United States
Houston Methodist Hospital Cancer Center
🇺🇸Houston, Texas, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Ordensklinikum Linz
🇦🇹Linz, Oberösterreich, Austria
Sarah Cannon Research Institute SCRI
🇺🇸Chattanooga, Tennessee, United States
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
🇧🇷Santo André, São Paulo, Brazil
Koo Foundation Sun Yan-Sen Cancer Center
🇨🇳Taipei, Taiwan
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Hainan General Hospital
🇨🇳Haikou, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Jiangxi Provincial Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
The Affiliated Cancer Hospital of Xinjiang Medical university
🇨🇳Urumqi, Xinjiang, China
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, Italy
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Summit Cancer Care, P.C.
🇺🇸Savannah, Georgia, United States
Florida Cancer Specialists
🇺🇸Saint Petersburg, Florida, United States
The Perth Blood Institute
🇦🇺West Perth, Australia
TOI Clinical Research
🇺🇸Cerritos, California, United States
California Cancer Associates for Research and Excellence
🇺🇸San Marcos, California, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Hopital de L'Enfant Jesus
🇨🇦Québec, Canada
Lakeland Regional Health Systems Inc
🇺🇸Lakeland, Florida, United States
TidalHealth Peninsula Regional, Inc.
🇺🇸Salisbury, Maryland, United States
Hematology Oncology Clinic
🇺🇸Baton Rouge, Louisiana, United States
Instituto do Câncer - Hospital São Vicente de Paulo
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Hospital Beneficência Portuguesa de São Paulo
🇧🇷Sao Paulo, Brazil
One Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa - Hospital Mae de Deus
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
Wu Han Tongji Hospital
🇨🇳Wuhan City, Hubei, China
Hospital Uopeccan - Centro de Pesquisa Clinica
🇧🇷Cascavel, Brazil
Royal Victoria Regional Health Centre
🇨🇦Barrie, Ontario, Canada
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷Sao Jose Rio Preto, Sao Paulo, Brazil
CeCim Biocinetic
🇨🇱Santiago, Región Metropolitana, Chile
Guangxi Medical University Affiliated Tumor Hospital
🇨🇳Nanning, Guangxi, China
Hopital de la Pitie Salpetriere
🇫🇷Paris, Cedex 13, France
Hôpital de Pontchaillou
🇫🇷Rennes, Cedex 9, France
Centre Henri Becquerel
🇫🇷Rouen Cedex, France
Uniklinik Köln
🇩🇪Kerpener, Köln, Germany
Middlemore Hospital
🇳🇿Otahuhu, New Zealand
The Catholic University of Korea-Seoul St. Mary's Hospital
🇰🇷Seocho-Gu, Seoul, Korea, Republic of
Dunedin Hospital
🇳🇿Dunedin, New Zealand
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Cataluña, Spain
Waikato Hospital
🇳🇿Hamilton, New Zealand
Szpital Wojewodzki w Opolu
🇵🇱Opole, Poland
Ege University Medical Faculty
🇹🇷Bornova, Izmir, Turkey
9 Eylul University Hospital
🇹🇷Balçova, İzmir, Turkey
Singleton Hospital
🇬🇧Swansea, United Kingdom
Istanbul University Istanbul Medical Faculty
🇹🇷Istanbul, Turkey
Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
Cancer Specialists of North Florida -St Augustine
🇺🇸Jacksonville, Florida, United States
Asclepes Research Centers Florida
🇺🇸Brooksville, Florida, United States
The James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Cancer Care Associates of York
🇺🇸York, Pennsylvania, United States
MultiCare Health System Institute for Research and Innovation
🇺🇸Spokane, Washington, United States
Baptist Healthcare System, Inc.
🇺🇸Louisville, Kentucky, United States
American Oncology Partners of Maryland, PA
🇺🇸Bethesda, Maryland, United States
Rabin Medical Center-Beilinson Campus
🇮🇱Petach-Tikva, Israel
Pacific Cancer Medical Center, Inc
🇺🇸Anaheim, California, United States
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
Stanford School of Medicine-Cancer Clinical Trials Office
🇺🇸Palo Alto, California, United States
Eastern Connecticut Hematology/Oncology Assoc.
🇺🇸Norwich, Connecticut, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Tulane Cancer Center Office of Clinical Research
🇺🇸New Orleans, Louisiana, United States
Novant Cancer Institute Charlotte
🇺🇸Charlotte, North Carolina, United States
Westchester Medical Center
🇺🇸Hawthorne, New York, United States
Lifespan Cancer Institute
🇺🇸Providence, Rhode Island, United States
Lumi Research
🇺🇸Kingwood, Texas, United States
Kelsey Research Foundation
🇺🇸Houston, Texas, United States
Summit Cancer Treatment Center
🇺🇸Spokane, Washington, United States
Instituto Alexander Fleming
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Clínica de Nefrología, Urología y Enfermedades Cardiovasculares
🇦🇷Santa Fe, Argentina
Hospital Italiano de Buenos Aires
🇦🇷ABB, Ciudad Autónoma De Buenos Aire, Argentina
UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
🇧🇷Botucatu, Sao Paulo, Brazil
Hospital das Clínicas da Faculdade de Medicina da USP
🇧🇷São Paulo, Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (USP) - HCFMRP
🇧🇷Ribeirão Preto, São Paulo, Brazil
Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP
🇧🇷Campinas, Sao Paulo, Brazil
Hospital Santa Marcelina
🇧🇷Sao Paulo, Brazil
Centro de Investigaciones Clínicas Viña del Mar (CIC)
🇨🇱Viña del Mar, Valparaíso, Chile
Southern Medical University Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
The 2nd Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Blood Institute of the Chinese Academy of Medical science
🇨🇳Tianjin, Tianjin, China
First Affiliated Hosp of College of Med, Zhejiang University
🇨🇳Hangzhou, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The Fourth Affiliated Hospital Zhejiang University School of Medicine
🇨🇳Yiwu, Zhejiang, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, China
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Fakultni Nemocnice Plzen
🇨🇿Plzen - Lochotin, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Fakultni Nemocnice Ostrava
🇨🇿Ostrava-Poruba, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
CHU de Nantes - Hotel Dieu
🇫🇷Nantes, Cedex 1, France
Centre Antoine Lacassagne
🇫🇷Nice, Nice Cedex 2, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, Cedex, France
CHRU De Tours
🇫🇷Tours, Tours Cedex 9, France
Centre Hospitalier Universitaire (Limoges) (CHU DUPUYTREN 1)
🇫🇷Limoges, France
CHD Vendee
🇫🇷La Roche sur Yon, France
Centre Hospitalier du Mans
🇫🇷Le Mans, France
GEFOS (Gesellschaft für onkologische Studien) Dortmund mbH
🇩🇪Dortmund, Nordrhein Westfalen, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Baden, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Sachsen, Germany
Gemeinschaftspraxis Haematologie und Onkologie
🇩🇪Dresden, Sachsen Anhalt, Germany
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Markusovszky Egyetemi Oktatokorhaz
🇭🇺Szombathely, Hungary
Hadassah Medical Center
🇮🇱Jerusalem, Israel
A.O.U. Citta' della Salute e della Scienza di Torino
🇮🇹Torino, Otago, Italy
IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST
🇮🇹Meldola, Forlì-Cesena, Italy
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Fondazione del Piemonte per l'Oncologia IRCCS Candiolo
🇮🇹Candiolo, Torino, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
🇮🇹Bologna, Italy
Azienda Unita Sanitaria Locale di Reggio Emilia
🇮🇹Reggio Emilia, Italy
Tokai University Hospital- Isehara Campus
🇯🇵Isehara, Kanagawa, Japan
Centro Ricerche Cliniche di Verona s.r.l.
🇮🇹Verona, Italy
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Yamagata University Hospital
🇯🇵Yamagata, Japan
Seoul National University Hospital
🇰🇷Seoul, Seoul, Korea, Korea, Republic of
Inje Univ Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
P3 Research
🇳🇿Newtown, Wellington, New Zealand
Centrum Medyczne Pratia Poznan
🇵🇱Skorzewo, Poznan, Poland
KO-MED Centra Kliniczne
🇵🇱Biała Podlaska, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Pomorskie, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Pratia MCM Krakow
🇵🇱Krakow, Poland
Szpital Uniwersytecki nr 2 im. dr Jana Biziela w BydgoszczyKlinika Hematologii
🇵🇱Bydgoszcz, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu Klinika Hematologii
🇵🇱Wrocław, Poland
Klinika Hematoonkologii i Transplantacji Szpiku
🇵🇱Lublin, Poland
Institut Català d'Oncologia de Girona (ICO Girona)
🇪🇸Girona, Cataluna, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Catalunya [Cataluña], Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Comunidad De, Spain
Hospital Costa Del Sol
🇪🇸Marbella, Malaga, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital De Gran Canaria Dr. Negrin
🇪🇸Las Palmas de Gran Canaria, Spain
Clinica Universitaria De Navarra
🇪🇸Madrid, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Chang Gung Memorial Hospital - Chiayi
🇨🇳Putz, Chiayi Hsien, Taiwan
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Chang Bing Show Chwan Memorial Hospital
🇨🇳Changhua, Taiwan
Bristol Haematology and Oncology Centre
🇬🇧Bristol, Bristol, City Of, United Kingdom
St Bartholomew's Hospital
🇬🇧London, London, City Of, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, Leicestershire, United Kingdom
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Privado De Comunidad
🇦🇷Mar Del Plata, Buenos Aires, Argentina
Hanusch Krankenhaus
🇦🇹Vienna, Austria
Sociedad de Investigaciones Médicas Limitada
🇨🇱Temuco, IX Región, Chile
Fundação Pio XII - Hospital de Câncer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States
VITAZ
🇧🇪Sint-Niklaas, Oost-Vlaanderen, Belgium
Centro de Estudios Clinicos SAGA
🇨🇱Providencia, Santiago, Chile
Acıbadem Maslak Hastanesi
🇹🇷Istanbul, Turkey
Centro Integrado de Oncologia de Curitiba
🇧🇷Curitiba, Paraná, Brazil
AZ Delta
🇧🇪Roeselare, West Flanders, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Gazi University Faculty of Medicine
🇹🇷Ankara, Yenimahalle, Turkey
Koc University American Hospital
🇹🇷Istanbul, Turkey
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
🇧🇷Curitiba, Paraná, Brazil
Ankara University Medicine Hospital
🇹🇷Mamak, Ankara, Turkey
Hospital De Navarra
🇪🇸Pamplona, Navarra, Spain
Castle Hill Hospital
🇬🇧Hull, East Riding Of Yorkshire, United Kingdom