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A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

NCT05254743 · Eli Lilly and Company
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Official title
A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314)
About this study
The purpose of Part 1 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. The purpose of Part 2 of this study evaluates pirtobrutinib monotherapy in treatment-naïve participants with CLL/SLL with 17p deletions. Participation could last up to six years for Part 1. Participation could last up to 2 years for Part 2.
Eligibility criteria
Inclusion Criteria: * Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria * Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing * 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) Exclusion Criteria: * 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 * Previous treatment for CLL/SLL - Part 1: Treatment-naïve and previously treated, except prior exposure to BTK inhibitor (covalent or noncovalent). Part 2: participants must be treatment naïve * 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
Enrollment target: 737 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-07-22
Estimated completion: 2028-01
Last updated: 2026-07-17
Interventions
Drug: PirtobrutinibDrug: Ibrutinib
Primary outcomes
  • 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) Part 1 (Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest] (approximately 3 years and 5 months))
  • 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) Part 2 (Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest (Approximately 2 years and 3 months))
Sponsor
Loxo Oncology, Inc. · industry
Contacts & investigators
ContactTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or · contact · LillyTrials@Lilly.com · 1-317-615-4559
ContactPhysicians interested in becoming principal investigators please contact · contact · clinical_inquiry_hub@lilly.com
InvestigatorCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST) · study_director, Eli Lilly and Company
All locations (143)
Pacific Cancer Medical Center, IncRecruiting
Anaheim, California, United States
TOI Clinical ResearchRecruiting
Cerritos, California, United States
Stanford School of Medicine-Cancer Clinical Trials OfficeRecruiting
Palo Alto, California, United States
California Cancer Associates for Research and ExcellenceActive Not Recruiting
San Marcos, California, United States
Florida Cancer SpecialistsRecruiting
Fort Myers, Florida, United States
Cancer Specialists of North Florida -St AugustineRecruiting
Saint Augustine, Florida, United States
Florida Cancer Specialists EastRecruiting
West Palm Beach, Florida, United States
Hematology Oncology ClinicActive Not Recruiting
Baton Rouge, Louisiana, United States
Tulane Cancer Center Office of Clinical ResearchActive Not Recruiting
New Orleans, Louisiana, United States
American Oncology Partners of Maryland, PARecruiting
Bethesda, Maryland, United States
St. Vincent Frontier Cancer CenterRecruiting
Billings, Montana, United States
Cancer Care Associates of YorkActive Not Recruiting
York, Pennsylvania, United States
Prisma Health Cancer InstituteActive Not Recruiting
Greenville, South Carolina, United States
Sarah Cannon Research Institute SCRIRecruiting
Nashville, Tennessee, United States
Kelsey Research FoundationActive Not Recruiting
Houston, Texas, United States
Lumi ResearchRecruiting
Kingwood, Texas, United States
Virginia Cancer InstituteRecruiting
Richmond, Virginia, United States
Medical Oncology Associates, PSRecruiting
Spokane, Washington, United States
MultiCare Health System Institute for Research and InnovationActive Not Recruiting
Spokane, Washington, United States
Alexander FlemingRecruiting
Ciudad Autónoma de Buenos Aire, Argentina
Hospital Privado De ComunidadActive Not Recruiting
Mar del Plata, Argentina
Clínica de Nefrología, Urología y Enfermedades CardiovascularesRecruiting
Santa Fe, Argentina
One Clinical ResearchActive Not Recruiting
Nedlands, Australia
Western Health, Sunshine HospitalActive Not Recruiting
St Albans, Australia
The Perth Blood InstituteRecruiting
West Perth, Australia
Hanusch KrankenhausActive Not Recruiting
Vienna, Austria
Universitaire Ziekenhuizen Leuven - Campus GasthuisbergRecruiting
Leuven, Belgium
VITAZRecruiting
Sint-Niklaas, Belgium
Fundação Pio XII - Hospital de Câncer de BarretosRecruiting
Barretos, Brazil
Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESPRecruiting
Botucatu, Brazil
Hemocentro UnicampRecruiting
Campinas, Brazil
Hospital Uopeccan - Centro de Pesquisa ClinicaRecruiting
Cascavel, Brazil
Centro Integrado de Oncologia de CuritibaActive Not Recruiting
Curitiba, Brazil
Hospital Erasto Gaertner - Liga Paranaense de Combate ao CâncerRecruiting
Curitiba, Brazil
Instituto do Câncer - Hospital São Vicente de PauloRecruiting
Passo Fundo, Brazil
Centro Gaucho Integrado - Mae de Deus CenterRecruiting
Porto Alegre, Brazil
Hospital de Clínicas de Ribeirão PretoRecruiting
Ribeirão Preto, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e OncologiaRecruiting
Santo André, Brazil
Centro Integrado de Pesquisa ClinicaRecruiting
São José do Rio Preto, Brazil
Hospital BPRecruiting
São Paulo, Brazil
Hospital da Clinicas da Faculdade de Medicina da USPRecruiting
São Paulo, Brazil
Hospital Santa MarcelinaRecruiting
São Paulo, Brazil
Royal Victoria Hospital-MontrealTerminated
Montreal, Canada
Hopital de L'Enfant JesusRecruiting
Québec, Canada
Cancer Care ManitobaActive Not Recruiting
Winnipeg, Canada
InmunocelActive Not Recruiting
Santiago, Chile
CeCim BiocineticActive Not Recruiting
Santiago, Chile
Sociedad de Investigaciones Médicas LimitadaRecruiting
Temuco, Chile
Centro de Investigaciones Clínicas Viña del Mar (CIC)Active Not Recruiting
Viña del Mar, Chile
The Second Xiangya Hospital of Central South UniversityActive Not Recruiting
Changsha, China
Hunan Cancer HospitalActive Not Recruiting
Changsha, China
Sun Yat-sen University Cancer CenterRecruiting
Guangzhou, China
Southern Medical University Nanfang HospitalRecruiting
Guangzhou, China
Hainan General HospitalActive Not Recruiting
Haikou, China
First Affiliated Hosp of College of Med, Zhejiang UniversityRecruiting
Hangzhou, China
The Second Affiliated Hospital of Zhejiang University School of MedicineActive Not Recruiting
Hangzhou, China
Anhui Provincial HospitalRecruiting
Hefei, China
The Second Hospital of Anhui Medical UniversityRecruiting
Hefei, China
Jiangxi Provincial Cancer HospitalActive Not Recruiting
Nanchang, China
Guangxi Medical University Affiliated Tumor HospitalRecruiting
Nanning, China
Fudan University Shanghai Cancer CenterRecruiting
Shanghai, China
Blood Institute of the Chinese Academy of Medical scienceActive Not Recruiting
Tianjin, China
Tianjin Medical University General HospitalActive Not Recruiting
Tianjin, China
Affiliated Cancer Hospital of Xinjiang Medical UniversityActive Not Recruiting
Ürümqi, China
Union Hospital Tongji Medical College Huazhong University of Science and TechnologyActive Not Recruiting
Wuhan, China
Wu Han Tongji HospitalActive Not Recruiting
Wuhan, China
The Fourth Affiliated Hospital Zhejiang University School of MedicineActive Not Recruiting
Yiwu, China
Fakultni nemocnice BrnoRecruiting
Brno, Czechia
Fakultni nemocnice Hradec KraloveRecruiting
Hradec Králové, Czechia
Fakultni Nemocnice OstravaRecruiting
Ostrava, Czechia
Fakultni Nemocnice PlzenRecruiting
Pilsen, Czechia
Fakultni nemocnice Kralovske VinohradyRecruiting
Prague, Czechia
Vseobecna fakultni nemocnice v PrazeRecruiting
Prague, Czechia
CHD VendeeRecruiting
La Roche-sur-Yon, France
Centre Hospitalier du MansRecruiting
Le Mans, France
Centre Hospitalier Universitaire (Limoges) (CHU DUPUYTREN 1)Recruiting
Limoges, France
CHU de Nantes - Hotel DieuRecruiting
Nantes, France
Centre Antoine LacassagneRecruiting
Nice, France
Hopital de la Pitie SalpetriereRecruiting
Paris, France
Centre Hospitalier Lyon SudRecruiting
Pierre-Bénite, France
Hôpital de PontchaillouRecruiting
Rennes, France
Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie RouenRecruiting
Rouen, France
CHRU De ToursRecruiting
Tours, France
Gemeinschaftspraxis für Hämatologie und Onkologie (Gefos)Active Not Recruiting
Dortmund, Germany
Onkologische Gemeinschaftspraxis / BAGRecruiting
Dresden, Germany
Universitaetsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik 1Active Not Recruiting
Dresden, Germany
Universitätsklinikum UlmActive Not Recruiting
Ulm, Germany
Debreceni Egyetem Orvos-es Egészsegtudomanyi CentrumRecruiting
Debrecen, Hungary
Markusovszky Egyetemi OktatokorhazActive Not Recruiting
Szombathely, Hungary
Hadassah Medical CenterRecruiting
Jerusalem, Israel
Tel Aviv Sourasky Medical CenterActive Not Recruiting
Tel Aviv, Israel
Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare ArrigoRecruiting
Alessandria, Italy
Policlinico Sant'Orsola MalpighiActive Not Recruiting
Bologna, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriRecruiting
Meldola, Italy
IRCCS Ospedale San RaffaeleRecruiting
Milan, Italy
Istituto Europeo di OncologiaRecruiting
Milan, Italy
Azienda Unita Sanitaria Locale di Reggio EmiliaActive Not Recruiting
Reggio Emilia, Italy
Kumamoto University HospitalActive Not Recruiting
Kumamoto, Japan
Yamagata University HospitalRecruiting
Yamagata, Japan
Dunedin HospitalActive Not Recruiting
Dunedin, New Zealand
Waikato HospitalActive Not Recruiting
Hamilton, New Zealand
Momentum Clinical ResearchRecruiting
Newtown, New Zealand
Middlemore Clinical TrialsRecruiting
Papatoetoe, New Zealand
KO-MED Centra KliniczneActive Not Recruiting
Biała Podlaska, Poland
Szpital Uniwersytecki nr 1 im. Antoniego JuraszaRecruiting
Bydgoszcz, Poland
Uniwersyteckie Centrum KliniczneRecruiting
Gdansk, Poland
Pratia Onkologia KatowiceRecruiting
Katowice, Poland
Pratia MCM KrakowRecruiting
Krakow, Poland
Klinika Hematoonkologii i Transplantacji Szpiku,Samodzielny Publiczny Szpital Kliniczny Nr 1Active Not Recruiting
Lublin, Poland
AIDPORT Sp. z o.o.Recruiting
Skórzewo, Poland
Uniwersytecki Szpital Kliniczny KlinikaRecruiting
Wroclaw, Poland
Inje Univ Busan Paik HospitalRecruiting
Busan, South Korea
The Catholic University of Korea-Seoul St. Mary's HospitalRecruiting
Seocho-Gu, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Samsung Medical CenterActive Not Recruiting
Seoul, South Korea
Hospital de la Santa Creu i Sant PauRecruiting
Barcelona, Spain
Hospital Clinic de BarcelonaActive Not Recruiting
Barcelona, Spain
Hospital Universitari Vall d'HebronRecruiting
Barcelona, Spain
Hospital Duran i ReynalsActive Not Recruiting
L'Hospitalet de Llobregat, Spain
Hospital Universitario Infanta Leonor-INTERNAL MEDRecruiting
Madrid, Spain
Hospital Universitario Ramón y CajalRecruiting
Madrid, Spain
Hospital Universitario Puerta de Hierro MajadahondaRecruiting
Majadahonda, Spain
Hospital Costa Del SolRecruiting
Marbella, Spain
Clinica Universitaria De NavarraRecruiting
Pamplona, Spain
Hospital De NavarraRecruiting
Pamplona, Spain
Hospital Universitario Marqués de ValdecillaRecruiting
Santander, Spain
Hospital Universitario Virgen MacarenaRecruiting
Seville, Spain
Hospital Universitario Virgen Del RocioRecruiting
Seville, Spain
Chang Bing Show Chwan Memorial HospitalRecruiting
Changhua, Taiwan
Chang Gung Memorial Hospital - ChiayiRecruiting
Chiayi County, Taiwan
National Cheng-Kung Uni. Hosp.Active Not Recruiting
Tainan, Taiwan
Koo Foundation Sun Yan-Sen Cancer CenterRecruiting
Taipei, Taiwan
Gazi University Faculty of MedicineActive Not Recruiting
Ankara, Turkey (Türkiye)
9 Eylul University HospitalActive Not Recruiting
Balçova, Turkey (Türkiye)
Ege ÜniversitesiActive Not Recruiting
Bornova, Turkey (Türkiye)
Istanbul University Istanbul Medicine FacultyRecruiting
Faith, Turkey (Türkiye)
American HospitalActive Not Recruiting
Istanbul, Turkey (Türkiye)
Acıbadem Maslak HastanesiCompleted
Istanbul, Turkey (Türkiye)
Ankara University Medicine HospitalRecruiting
Mamak, Turkey (Türkiye)
Bristol Haematology and Oncology CentreRecruiting
Bristol, United Kingdom
HOPE CentreActive Not Recruiting
Leicester, United Kingdom
St Bartholomew's HospitalActive Not Recruiting
London, United Kingdom
Singleton HospitalRecruiting
Swansea, United Kingdom
A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) · TrialPath