A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

NCT05023980 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: 18088J2N-OX-JZNPLOXO-BTK-20023
• Study Type: interventional
• Target: 309
• Locations: 19 countries
• Sites: 105

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

BTKi; BTK Inhibitor; Hematologic Disease; Lymphoma, non-Hodgkin's; Lymphoma, B-cell

Outcome Measures

Primary Outcomes (1)

• To evaluate progression-free survival (PFS) of pirtobrutinib (Arm A) compared to bendamustine and rituximab (Arm B)

  Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Response Criteria

  Up to approximately 5 years

Secondary Outcomes (7)

• To evaluate the effectiveness of Arm A compared to Arm B: Progression-free survival (PFS)

  Up to approximately 5 years

• To evaluate the effectiveness of Arm A compared to Arm B: Overall survival (OS)

  Up to approximately 5 years

• To evaluate the effectiveness of Arm A compared to Arm B: Time to next treatment (TTNT)

  Up to approximately 5 years

• To evaluate the effectiveness of Arm A compared to Arm B: Overall response rate (ORR)

  Up to approximately 5 years

• To evaluate the effectiveness of Arm A compared to Arm B: Duration of Response (DOR)

  Up to approximately 5 years

Study Arms (2)

Arm A (Pirtobrutinib)

EXPERIMENTAL

Pirtobrutinib administered orally

Drug: Pirtobrutinib

Arm B (BR)

ACTIVE COMPARATOR

Bendamustine plus rituximab administered intravenously (IV)

Drug: Bendamustine; Drug: Rituximab

Interventions

Pirtobrutinib DRUG

Oral

Also known as: LOXO-305, LY3527727

Arm A (Pirtobrutinib)

Bendamustine DRUG

IV

Also known as: Treanda, Treakisym, Ribomustin, Levact

Arm B (BR)

Rituximab DRUG

IV

Also known as: Rituxan, MabThera, Truxima, Riabni, Ruxience

Arm B (BR)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Loxo Oncology, Inc.: lead
• Eli Lilly and Company: collaborator

Study Sites (108)

California Research Institute

Los Angeles, California, 90027, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Oncology-Hematology Associates of West Broward

Coral Springs, Florida, 33065, United States

Location

New Jersey Center for Cancer Research

Brick, New Jersey, 08724, United States

Location

Clinical Research Alliance, Inc.

Westbury, New York, 11590, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Westmead Hospital

Wentworthville, New South Wales, 2145, Australia

Location

Peninsula Private Hospital

Frankston, Victoria, 3199, Australia

Location

Uniklinikum Salzburg

Salzburg, 5020, Austria

Location

Klinik Ottakring

Vienna, 1160, Austria

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

Location

Centro Gaucho Integrado - Mae de Deus Center

Porto Alegre, Rio Grande do Sul, 90110270, Brazil

Location

Hemocentro Unicamp

Campinas, São Paulo, 13083-878, Brazil

Location

Fundação Doutor Amaral Carvalho

Jaú, São Paulo, 17210120, Brazil

Location

UMHAT "Sveti Georgi" EAD

Plovdiv, 4000, Bulgaria

Location

UMHAT 'Sv. Ivan Rilski', EAD

Sofia, 1431, Bulgaria

Location

"SHATHD" EAD, Sofia

Sofia, 1797, Bulgaria

Location

UMHAT - Prof. Dr. Stoyan Kirkovich" AD

Stara Zagora, 6003, Bulgaria

Location

Anhui Provincial Cancer Hospital

Hefei, Anhui, 233004, China

Location

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, 010050, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Shengjing Hospital of China Medical University

Shenyany, Liaoning, 110022, China

Location

Jiangsu Province Hospital

Nanjing, Nanjing, 210029, China

Location

Shanghai Tongren Hospital

Changning District, Shanghai Municipality, 200050, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Institute of hematology&blood disease hospital

Tianjin, Tianjin Municipality, 300020, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

The First People's Hospital of Hangzhou Linping District

Hangzhou, Zhejiang, 311100, China

Location

Beijing Hospital

Beijing, 100730, China

Location

Chongqing Cancer Hospital

Chongqing, 400030, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Fakultni nemocnice Brno

Brno, 62500, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Hospitalier Le Mans

Le Mans, 72000, France

Location

Debreceni Egyetem Orvos-es Egészsegtudomanyi Centrum

Debrecen, 4032, Hungary

Location

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, 8000, Hungary

Location

Irccs Crob

Rionero in Vulture, Potenza, 85028, Italy

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C

Milan, 20162, Italy

Location

Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)

Monza, 20900, Italy

Location

Azienda Ospedale Maggiore Della Carita

Novara, 28100, Italy

Location

Istituto di Ematologia-C.R.E.O. (Centro di Ricerche Emato-Oncologich)

Perugia, 06132, Italy

Location

Ospedale Santa Maria delle Croci

Ravenna, 48020, Italy

Location

Azienda Ospedaliera Santa Maria Terni

Terni, 05100, Italy

Location

Azienda sanitaria integrata università di Trieste

Trieste, 34125, Italy

Location

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Chiba Cancer Center

Chiba, Chiba, 260-8717, Japan

Location

Fukui Medical University Hospital

Yoshida-Gun, Fukui, 910-1193, Japan

Location

Hokuyukai Sapporo Hokuyu Hospital

Sapporo, Hokkaido, 0030006, Japan

Location

Kochi Medical School Hospital

Nankoku, Kochi, 783-8505, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

NHO Sendai Medical Center

Sendai, Miyagi, 9838520, Japan

Location

Dokkyo Medical University - Koshigaya Hospital

Koshigaya, Saitama, 343 8555, Japan

Location

University of Yamanashi Hospital

Chūō, Yamanshi, 409-3821, Japan

Location

Aomori Prefectural Centeral Hospital

Aomori, 030-8553, Japan

Location

JCHO Kyushu Hospital

Fukoka-ken, 806 8501, Japan

Location

North Shore Hospital, Haematology Research

Takapuna, Auckland, 0622, New Zealand

Location

Tauranga Hospital

Tauranga, Bay of Plenty, 3112, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Middlemore Clinical Trials

Papatoetoe, 2025, New Zealand

Location

Wojewodzki Szpital Specjalistyczny

Iwaszkiewicza 5, Legnica, 59-220, Poland

Location

Klinika Hematoonkologii i Transplantacji Szpiku SPSK1 Lublin

Lublin, Lubelskie V, 20081, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, 80214, Poland

Location

Centrum Medyczne Pratia Poznan

Skorzewo, Poznan, 60 185, Poland

Location

KO-MED Centra Kliniczne

Biała Podlaska, 21500, Poland

Location

Szpital Uniwersytecki nr 1 im. Antoniego Jurasza

Bydgoszcz, 85-168, Poland

Location

Pratia Onkologia Katowice

Katowice, 40519, Poland

Location

Pratia MCM Krakow

Krakow, 30727, Poland

Location

Centrum Onkologii Ziemi Lubelskiej

Lublin, 20-090, Poland

Location

Nasz Lekarz Osrodek Badan Klinicznych

Torun, 87-100, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Cuire - Państwowy Instytut Badawczy

Warsaw, 02781, Poland

Location

Uniwersytecki Szpital Kliniczny Klinika

Wroclaw, 50-367, Poland

Location

Centro Clínico Académico - Braga (2CA-Braga) (Hospital de Braga)

Braga, 4710-243, Portugal

Location

Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria

Lisbon, 1649035, Portugal

Location

Instituto Português de Oncologia do Porto Francisco Gentil, EPE

Porto, 4200-072, Portugal

Location

Spitalul Clinic Municipal Filantropia Craiova

Craiova, Dolj, 200143, Romania

Location

Institutul Clinic Fundeni - Centrul de Hematologie si Transplant Medular

Bucharest, 022328, Romania

Location

Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca

Cluj-Napoca, 400015, Romania

Location

Institutului Regional de Oncologie IASI

Iași, 700483, Romania

Location

Academician I.P. Pavlov First St-Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

Gachon University Gil Medical Center

Namdong-gu, Incheon-gwangyeoksi [Incheon], 21565, South Korea

Location

The Catholic University of Korea-Seoul St. Mary's Hospital

Seocho-Gu, Seoul, 06591, South Korea

Location

Seoul National University Hospital

Seoul, Seoul, Korea, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, Seoul-teukbyeolsi [Seoul], 03722, South Korea

Location

Samsung Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], 06351, South Korea

Location

Inje Univ Busan Paik Hospital

Busan, 47392, South Korea

Location

Hospital Universitario HM Sanchinarro

Madrid, Madrid, Comunidad de, 28050, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario Virgen de Valme

Seville, 41014, Spain

Location

Chang Bing Show Chwan Memorial Hospital

Changhua, 50544, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Chang Gung Memorial Hospital - Linkou

Taoyuan, 333, Taiwan

Location

Birmingham Heartlands Hospital

Birmingham, England, B9 5SS, United Kingdom

Location

Related Publications (2)

• Eyre TA, Hess LM, Masoudi E, Jen MH, Abhyankar S, Graham-Clarke PL, Bhandari NR, Maguire P, Winfree KB, Tracey M, Taipale KL, Davids MS. Efficacy of Pirtobrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2026 Feb 18;18(4):660. doi: 10.3390/cancers18040660.

  PMID: 41749915 DERIVED

• Jurczak W, Kwiatek M, Czyz J, Roberto de Mattos E, Eom KS, Egle A, Panovska A, Popova ZG, Shih HJ, Casado Montero LF, Sportoletti P, Hua VM, D'Olimpio JT, Iida S, Ito R, Bao K, Fink A, Su W, Ruppert AS, Levy A, Wrobel T. BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. J Clin Oncol. 2026 Feb 20;44(6):466-475. doi: 10.1200/JCO-25-02380. Epub 2025 Dec 9.

  PMID: 41363773 DERIVED

Related Links

• A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN CLL-313)

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Interventions

pirtobrutinib; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: August 27, 2021
• Study Start: September 23, 2021
• Primary Completion: July 11, 2025
• Study Completion (Estimated): October 1, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (12); IT (12); AU (2); BR (5); KR (6); BU (4); RU (1); TW (4); CZ (2); HU (3); GB (1); US (5); PT (3); CN (19); JP (11); FR (1); NZ (4); ES (6); RO (4)