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)

NCT04965493 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: 18087J2N-OX-JZNOLOXO-BTK-20022
• Study Type: interventional
• Target: 600
• Locations: 23 countries
• Sites: 176

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

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

  Up to approximately 5 years

Secondary Outcomes (7)

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

  Up to approximately 5 years

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

  Up to approximately 5 years

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

  Up to approximately 5 years

• To evaluate the efficacy of Arm A compared to Arm B: Event-free survival (EFS)

  Up to approximately 5 years

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

  Up to approximately 5 years

Study Arms (2)

Arm A (PVR)

EXPERIMENTAL

Fixed duration pirtobrutinib in combination with venetoclax and rituximab

Drug: Pirtobrutinib; Drug: Venetoclax; Drug: Rituximab

Arm B (VR)

ACTIVE COMPARATOR

Venetoclax with rituximab

Drug: Venetoclax; Drug: Rituximab

Interventions

Pirtobrutinib DRUG

Oral

Also known as: LOXO-305, LY3527727

Arm A (PVR)

Venetoclax DRUG

Oral

Also known as: Venclexta, Venclyxto

Arm A (PVR); Arm B (VR)

Rituximab DRUG

Intravenous (IV)

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

Arm A (PVR); Arm B (VR)

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
• 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)

You may not qualify if:

• 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:

Sponsors & Collaborators

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

Study Sites (176)

Ironwood Physicians, Ironwood Cancer and Research Centers

Chandler, Arizona, 85224, United States

Location

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Scripps Mercy Hospital

San Diego, California, 92111, United States

Location

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

Stamford Hospital

Stamford, Connecticut, 06902, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916-2233, United States

Location

Cancer Specialists of North Florida -St Augustine

Saint Augustine, Florida, 32086, United States

Location

Florida Cancer Specialists East

West Palm Beach, Florida, 33401, United States

Location

Mission Cancer and Blood

Des Moines, Iowa, 50309, United States

Location

Pikeville Medical Center, Inc.

Pikeville, Kentucky, 41501, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905-0002, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Novant Cancer Institute Charlotte

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Regional Medical Oncology Center

Wilson, North Carolina, 27893, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Oncology Associates of Bridgeport P.C.

Eugene, Oregon, 97401, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

USO - Texas Oncology - San Antonio

San Antonio, Texas, 78240, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908-0816, United States

Location

Virginia Cancer Specialists, PC - Lee Highway

Fairfax, Virginia, 22031, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0070, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98104-2092, United States

Location

Swedish Cancer Institute; STE 1020

Seattle, Washington, 98104, United States

Location

Northwest Cancer Specialists PC

Vancouver, Washington, 98684, United States

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Peninsula Private Hospital

Frankston, 3199, Australia

Location

Royal Hobart Hospital

Hobart, 7000, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

St Vincent's Hospital

Melbourne, 3065, Australia

Location

Sir Charles Gairdner Hospital

Perth, 6009, Australia

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Groupe Jolimont

La Louvière, 7100, Belgium

Location

CHU UCL Namur site Godinne

Yvoir, 5530, Belgium

Location

Foothills Medical Centre

Calgary, T2N 2T9, Canada

Location

Cross Cancer Institute

Edmonton, T6G 1Z2, Canada

Location

Jewish General Hospital

Montreal, H3T 1E2, Canada

Location

Sunnybrook Research Institute

Toronto, M4N 3M5, Canada

Location

BC Cancer Vancouver

Vancouver, V5Z 4E6, Canada

Location

Cancer Care Manitoba

Winnipeg, R3A 1M3, Canada

Location

Peking University First Hospital

Beijing, 100034, China

Location

Peking University People's Hospital

Beijing, 100044, China

Location

The Second Xiangya Hospital of Central South University

Changsha, 410008, China

Location

Chongqing Cancer Hospital

Chongqing, 400030, China

Location

Fujian Provincial Cancer Hospial

Fuzhou, 350014, China

Location

Cancer Center of Guangzhou Medical University

Guangzhou, 510000, China

Location

First Affiliated Hosp of College of Med, Zhejiang University

Hangzhou, 310003, China

Location

The First Affiliated Hospital of Anhui Medical University

Hefei, 230022, China

Location

The First Affiliated Hospital Of University Of South China

Hengyang, 421001, China

Location

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, 010050, China

Location

The First People's Hospital of Yunnan Province

Kunming, 650034, China

Location

Jiangxi Provincial Cancer Hospital

Nanchang, 330029, China

Location

Jiangsu Province Hospital

Nanjing, 210029, China

Location

Guangxi Medical University Affiliated Tumor Hospital

Nanning, 530021, China

Location

Nantong Tumor Hospital

Nantong, 226000, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, 266555, China

Location

Shanghai Jiaotong University School of Medicine Ruijin Hospital

Shanghai, 200025, China

Location

Shanghai Tongren Hospital

Shanghai, 200336, China

Location

Shengjing Hospital of China Medical University

Shenyang, 110004, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, 300060, China

Location

Wuhan Union Hospital

Wuhan, 430022, China

Location

Wu Han Tongji Hospital

Wuhan, 430030, China

Location

Wuxi People's Hospital

Wuxi, 214023, China

Location

Yichang Central People's Hospital

Yichang, 443003, China

Location

Henan Provincial People's Hospital

Zhengzhou, 450003, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Zhongshan City People's Hospital

Zhongshan, 528403, China

Location

Fakultni nemocnice Brno

Brno, 62500, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 10034, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12808, Czechia

Location

Rigshospitalet

Copenhagen, 2200, Denmark

Location

Centre Hospitalier du Mans

Le Mans, 72000, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois

Morvan, 54511, France

Location

CHU de Nantes - Hotel Dieu

Nantes, 44093, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hopital de la Pitie Salpetriere

Paris, 75651, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Pole Regionalde Cancérologie(CHU de Poitiers)

Politiers, 86021, France

Location

Hôpital de Pontchaillou

Rennes, 35033, France

Location

Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen

Rouen, 76038, France

Location

ICANS_Institut de Cancerologie Strasbourg Europe

Strasbourg, 67033, France

Location

CHRU De Tours

Tours, 37044, France

Location

Klinikum Chemnitz GmbH

Chemnitz, 09131, Germany

Location

Universtitätsklinikum Essen AöR

Essen, 45147, Germany

Location

Uniklinik Köln

Kerpener, 50937, Germany

Location

München Klinik Schwabing

Koelner Platz 1, 80804, Germany

Location

Universitätsklinikum Leipzig AöR Klinik und Poliklinik für Hämatologie

Leipzig, 04103, Germany

Location

Unimedizin RostockZIM III -Haemtologie

Rostock, 18057, Germany

Location

Gemeinschaftspraxis Dres. Schöttker & Pretscher, z.Hd. Sophie Enz

Würzburg, 97080, Germany

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Mater Misericordiae Hospital

Dublin, Ireland

Location

University Hospital Waterford

Waterford, X91 ER8E, Ireland

Location

Bnai Zion Medical Center

Haifa, 3339419, Israel

Location

Galilee Medical Center

Nahariya, 22100, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center

Rehovot, 7610001, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

IRCCS - AOU di Bologna

Bologna, 40138, Italy

Location

Azienda Ospedaliera Pugliese Ciaccio

Catanzaro, 88100, Italy

Location

AOU Arcispedale Sant'Anna

Cona, 44124, Italy

Location

Ospedale Santa Croce e Carle

Cuneo, 12100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C

Milan, 20162, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

A.O.U. di Modena

Modena, 41224, Italy

Location

Azienda Ospedale Maggiore Della Carita

Novara, 28100, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

Policlinico Umberto I - Haematology

Rome, 00161, Italy

Location

A.O.U. Citta' della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Tokyo Medical and Dental University Hospital

Bunkyō City, 113-8519, Japan

Location

National Cancer Center Hospital East

Chiba-Ken, 277 8577, Japan

Location

University of Yamanashi Hospital

Chūō, 409-3821, Japan

Location

National Cancer Center Hospital

Chūōku, 104-0045, Japan

Location

University of Fukui Hospital

Fukui, 9101193, Japan

Location

Japanese Foundation for Cancer Research

Kōtō City, 135-8550, Japan

Location

Kyoto Furitsu Medical University Hospital

Kyoto, 602-8566, Japan

Location

Kochi Medical School Hospital

Nankoku, 783-8505, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Osaka City General Hospital

Osaka, 534-0021, Japan

Location

Akershus Universitetssykehus

Nordbyhagen, 1474, Norway

Location

St-Olavs Hospital

Trondheim, 7006, Norway

Location

Szpitale Pomorskie Sp. z o. o.

Gdynia, 81-519, Poland

Location

Pratia Onkologia Katowice

Katowice, 40519, Poland

Location

Pratia MCM Krakow

Krakow, 30-510, Poland

Location

Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii

Lodz, 93510, Poland

Location

Klinika Hematoonkologii i Transplantacji Szpiku,Samodzielny Publiczny Szpital Kliniczny Nr 1

Lublin, 20-081, Poland

Location

MICS Centrum Medyczne Torun

Torun, 87-100, Poland

Location

Instytut Hermatologii I Transfuzjologii

Warsaw, Poland

Location

Singapore General Hospital

Singapore, 169078, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 8041, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, 28031, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Puerta De Hierro

Majadahonda, 28222, Spain

Location

Hospital Costa Del Sol

Marbella, 29600, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital Universitario de Toledo

Toledo, 45007, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Skanes Universitetssjukhus, Hematoloaimottagningen

Lund, 22185, Sweden

Location

Karolinska Universitetssjukhuset i Solna

Stockholm, 17176, Sweden

Location

Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Related Links

• 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) (BRUIN CLL-322)

MeSH Terms

Conditions

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

Interventions

pirtobrutinib; venetoclax; 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)

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.

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: July 16, 2021
• Study Start: September 20, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (41); JP (10); DE (7); IL (5); NO (2); IT (13); IE (2); CH (2); DK (1); HU (2); CA (6); FR (12); PL (7); AU (6); BE (3); SG (1); KR (2); ES (14); CZ (4); GB (6); CN (27); TW (1); SE (2)