Study of LOXO-305 (Pirtobrutinib) Versus Investigator's Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

NCT04666038 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: 18073J2N-OX-JZNNLOXO-BTK-20020
• Study Type: interventional
• Target: 238
• Locations: 23 countries
• Sites: 225

Brief Summary

This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four years, and possibly longer, if the disease does not progress.

Conditions

Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Keywords

Hematologic Disease; Lymphoma, non-Hodgkin's; Lymphoma, B-cell; Lymphoma; Bruton's tyrosine kinase inhibitor; Ibrutinib; Acalabrutinib; Zanubrutinib; Pirtobrutinib

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)

  PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an IRC according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018.

  Randomization to Disease Progression or Death Due to Any Cause (Up to 29 Months)

Secondary Outcomes (7)

• PFS Assessed by Investigator

  Randomization to Disease Progression or Death Due to Any Cause (Up to 36 Months)

• Overall Survival (OS)

  Randomization to Death from Any Cause (Up to 36 months)

• Time to Next Treatment (TTNT)

  Randomization to Subsequent Anticancer Therapy, Therapy of Pirtobrutinib or Death Due to Any Cause (Up to 36 Months)

• Event Free Survival (EFS)

  Randomization to Disease Progression, Subsequent Anticancer Therapy, Unacceptable Toxicity Leading to Treatment Discontinuation, or Death Due to Any Cause (Up to 36 Months)

• Percentage of Participants With Overall Response Rate (ORR) Assessed by Investigator

  Randomization to Subsequent Anticancer Therapy, Disease Progression or Death Due to Any Cause (Up to 36 Months)

Study Arms (2)

Arm A - Pirtobrutinib

EXPERIMENTAL

Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.

Drug: Pirtobrutinib

Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab

ACTIVE COMPARATOR

Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m\^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m\^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m\^2 every 4 weeks (Q4W) or 70 mg/m\^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m\^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m\^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Drug: Idelalisib; Drug: Bendamustine; Drug: Rituximab

Interventions

Pirtobrutinib DRUG

Oral Pirtobrutinib

Also known as: LOXO-305, LY3527727

Arm A - Pirtobrutinib

Idelalisib DRUG

Oral

Also known as: Zydelig

Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab

Bendamustine DRUG

IV

Also known as: Treanda, Treakisym, Ribomustin, Levact

Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab

Rituximab DRUG

IV

Also known as: Rituxan, MabThera, Truxima

Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab

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 as defined by iwCLL 2018 criteria.
• Previously treated with a covalent BTK inhibitor.
• Eastern Cooperative Oncology Group (ECOG) 0-2.
• Absolute neutrophil count ≥ 0.75 × 10\^9/L without granulocyte-colony-stimulating factor support, or ≥ 0.50 × 10\^9/L in patients with documented bone marrow involvement considered to impair hematopoiesis. Granulocyte-colony-stimulating factor support is permitted in patients with documented bone marrow involvement.
• Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Transfusion support is permitted in patients with bone marrow involvement.
• Platelets ≥ 50 × 10\^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75 × 10\^9/L. Patients may enroll below these thresholds if the Investigator determines the cytopenia is related to bone marrow involvement considered to impair hematopoiesis. Patients with a platelet count \< 30 x 10\^9/L are excluded.
• AST and ALT ≤ 3.0 x upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 x ULN.
• Estimated creatinine clearance of ≥ 30 mL/min.

You may not qualify if:

• Known or suspected Richter's transformation at any time preceding enrollment.
• Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.
• Ongoing drug-induced liver injury.
• Active uncontrolled auto-immune cytopenia.
• Significant cardiovascular disease.
• History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor-modified T cells (CAR-T) therapy within the past 60 days.
• Active hepatitis B or hepatitis C.
• Known active cytomegalovirus (CMV) infection.
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
• Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.
• Clinically significant active malabsorption syndrome or inflammatory bowel disease
• Prior exposure to 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.
• Vaccination with a live vaccine within 28 days prior to randomization.

Sponsors & Collaborators

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

Study Sites (232)

Southern Cancer Center, P.C.

Daphne, Alabama, 36526, United States

Location

Mitchell Cancer Institute -University of South Alabama

Mobile, Alabama, 36604, United States

Location

Palo Verde Hematology Oncology

Glendale, Arizona, 85304, United States

Location

Arizona Oncology Associates, P.C. - HOPE

Tucson, Arizona, 85711, United States

Location

Orange Coast Memorial Medical Center

Fountain Valley, California, 92708, United States

Location

California Research Institute

Los Angeles, California, 90027, United States

Location

Rocky Mountain Cancer Center

Aurora, Colorado, 80012, United States

Location

Medical Oncology Hematology Consultants, PA

Newark, Delaware, 19713, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Cancer Specialists of North Florida -St Augustine

Jacksonville, Florida, 32256, United States

Location

Oncology-Hematology Associates of West Broward

Tamarac, Florida, 33321, United States

Location

WellStar Health System

Marietta, Georgia, 30060, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Illinois Cancer Specialists-Niles

Niles, Illinois, 60714, United States

Location

Community Health Network

Indianapolis, Indiana, 46250, United States

Location

Arnett Cancer Center

Lafayette, Indiana, 47904, United States

Location

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40563, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Mercy Health-Paducah Medical Oncology and Hematology

Paducah, Kentucky, 42003, United States

Location

Cancer Center Office of Clinical Research

New Orleans, Louisiana, 70112, United States

Location

Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Ascension St. John Hospital

Grosse Pointe Woods, Michigan, 48236, United States

Location

Minnesota Oncology/Hematology PA

Saint Paul, Minnesota, 55102, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Nebraska Hematology-Oncology

Lincoln, Nebraska, 68506, United States

Location

New Jersey Center for Cancer Research

Brick, New Jersey, 08724, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Clinical Research Alliance, Inc.

Westbury, New York, 11590, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45236, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Carolina Blood and Cancer Care Associates

Rock Hill, South Carolina, 29732, United States

Location

Texas Oncology - Amarillo

Amarillo, Texas, 79106, United States

Location

Texas Oncology Cancer Center

Austin, Texas, 78705, United States

Location

Texas Oncology - Medical City Dallas

Dallas, Texas, 75230, United States

Location

Texas Oncology - Dallas Presbyterian Hospital

Dallas, Texas, 75231, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Texas Oncology Fort Worth

Fort Worth, Texas, 76104, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - McAllen

McAllen, Texas, 78503, United States

Location

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Virginia Cancer Specialists, PC

Gainesville, Virginia, 20155, United States

Location

Oncology and Hematology Associates of Southwest Virginia Inc

Roanoke, Virginia, 24014, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

St Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

The St. George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Ingham Institute of Medical Research

Liverpool, New South Wales, NSW2170, Australia

Location

Westmead Hospital

Wentworthville, New South Wales, 2145, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Uniklinikum Salzburg

Salzburg, Osterreich, 5020, Austria

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, 4020, Austria

Location

Medizinische Universität Wien

Vienna, 1090, Austria

Location

CHR Verviers-Onco

Verviers, Liege, 4800, Belgium

Location

VITAZ

Sint-Niklaas, Oost-Vlaanderen, B-9100, Belgium

Location

AZ Delta

Roeselare, West Flanders, 8800, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Groupe Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

AZ St-Elisabeth

Herentals, 2200, Belgium

Location

Clinique Saint Pierre Ottignies

Ottignies, 1340, Belgium

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Southlake Regional Health Centre

Newmarket, Ontario, L3Y 2P9, Canada

Location

Princess Margaret Hospital (Ontario)

Toronto, Ontario, M5G 1Z5, Canada

Location

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Xuanwu Hospital Capital Medical University

Xicheng District, Beijing Municipality, 100053, China

Location

Gansu Province Cancer Hospital

Lanzhou, Gansu, 730050, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

Southern Medical University Nanfang Hospital

Guangzhou, Guangdong, 510515, China

Location

Hainan Province People's Hospital

Haikou, Hainan, 570100, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

The Affiliated Hospital of Xuzhou Medical College

Xuzhou, Jiangsu, 221006, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Location

Affiliated Tumor Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, 830002, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Zhejiang Provincial Taizhou Hospital

Linhai, Zhejiang, 317000, China

Location

Beijing Hospital

Beijing, 100730, China

Location

Shanghai Jiaotong University School of Medicine Ruijin Hospital

Shanghai, 200025, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Blood Institute of the Chinese Academy of Medical science

Tianjin, 300020, China

Location

University Hospital Split

Split, 21000, Croatia

Location

Division of Hematology, Dept. of Internal Medicine, University Hospital Centre Zagreb

Zagreb, Croatia

Location

Fakultni nemocnice Brno

Brno, 62500, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12808, Czechia

Location

CHU De Grenoble Hopital Albert Michallon

Grenoble, Cedex 09, 38043, France

Location

Hospital AVICENNE

Bobigny, Cedex, 93 009, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Cedex, 69495, France

Location

CHD Vendee

La Roche-sur-Yon, La Roche Sur Yon, 85000, France

Location

Chu Nimes/Institut De Cancerologie Du Gard

Nîmes, Nimes, 30900, France

Location

Pole Regionalde Cancérologie(CHU de Poitiers)

Politiers, Politiers, 86021, France

Location

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

Rouen, Seine-Maritime, 76038, France

Location

CHRU De Tours

Tours, Tours Cedex 9, 37044, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64109, France

Location

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, 33076, France

Location

CHRU de Brest - Hôpital Morvan

Brest, 29609, France

Location

Centre Hospitalier du Mans

Le Mans, 72000, France

Location

Hopital Saint Vincent De Paul

Lille, 59020, France

Location

Ch Perpignan

Perpignan, 66046, France

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Uniklinik Köln

Kerpener, Köln, 50937, Germany

Location

Universitätsmedizin Mainz III. Medizinische Klinik und Poliklinik

Langenbeckstraße 1, Mainz, D- 55131, Germany

Location

München Klinik Schwabing

Koelner Platz 1, München, 80804, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, Schleswig-Holstein, 24105, Germany

Location

Lübecker Onkologische Schwerpunktpraxis

Lübeck, Schleswig-Holstein, 23562, Germany

Location

Charité Campus Virchow-Klinikum

Berlin, 12203, Germany

Location

Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet

Budapest, 1097, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

University of Pecs 1st. Internalmedicin Clinic Dept

Pécs, 7624, Hungary

Location

St James's Hosptial

Dublin, D08 NHY1, Ireland

Location

Beaumont Hospital, Dublin

Dublin, DUBLIN 9, Ireland

Location

Mater Misericordiae Hospital

Dublin, Ireland

Location

Rabin Medical Center

Petah Tikva, Central District, Israel

Location

Soroka Medical Center

Beersheba, 8457108, Israel

Location

Laniado Medical Center

Netanya, 4244916, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Carmel Hospital

Haifa, Ḥeifā, 3436212, Israel

Location

Irccs Istituto Tumori Giovanni Paolo Ii

Viale Orazio Flacco, Bari, 70124, Italy

Location

ASST-Monza -U.O Ematologia Adulti

Monza (MB) -Settore E, Piano 2, 20900, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, PI, 56126, Italy

Location

Irccs Crob

Rionero in Vulture, Potenza, 85028, Italy

Location

AULSS8 Berica-Ospedale S.Bortolo

Vicenza, Veneto, 36100, Italy

Location

Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo

Alessandria, 15100, Italy

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

ASST Spedali Civili - Università degli Studi

Brescia, 25123, Italy

Location

A.O.U. Policlinico G.Rodolico - S. Marco

Catania, 95123, Italy

Location

Azienda Ospedaliera Pugliese Ciaccio

Catanzaro, 88100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

Ospedale Papardo

Messina, 98158, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C

Milan, 20162, Italy

Location

A.O.U. di Modena

Modena, 41124, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, 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

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

Roma, 00168, Italy

Location

Azienda Ospedaliera Santa Maria Terni

Terni, 05100, Italy

Location

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

Torino, 10126, Italy

Location

Az. Osp. "Card G Panico"

Tricase, 4 - 73039, Italy

Location

Azienda Sanitaria Universitaria Giuliano Isontina

Trieste, 34125, Italy

Location

Ospedale Policlinico Giambattista Rossi, Borgo Roma

Verona, 37134, Italy

Location

Nagoya Medical Center

Nagoya, Aichi-ken, 460-0001, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Ogaki Municipal Hospital

Ogaki-shi, Gifu, 503-8502, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

Location

Tokai University Hospital- Isehara Campus

Isehara, Kanagawa, 259-1143, 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, 983-8520, Japan

Location

Kindai University Hospital

Osaka Sayama-shi, Osaka, 589 8511, Japan

Location

Saitama Medical Center

Kawagoe, Saitama, 350-8550, Japan

Location

Japanese Foundation for Cancer Research

Koto, Tokyo, 135-8550, Japan

Location

NTT Medical Center Tokyo

Shinagawa-Ku, Tokyo, 141-8625, Japan

Location

JCHO Kyushu Hospital

Fukoka-ken, 806 8501, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Wojewodzki Szpital Specjalistyczny

Iwaszkiewicza 5, Legnica, 59-220, Poland

Location

Centrum Onkologii Ziemi Lubelskiej

Lublin, Lublin Voivodeship, 20-081, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Szpitale Pomorskie Sp. z o. o.

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im.ks.B.Markiewicza

Brzozów, 36-200, Poland

Location

Szpital Uniwersytecki nr 2 im. dr Jana Biziela w BydgoszczyKlinika Hematologii

Bydgoszcz, 85-168, 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

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Oddzial Hematologiczny, Specjalistyczny Szpital im. dra Sokołowskiego w Wałbrzychu

Wałbrzych, 58-309, Poland

Location

Uniwersytecki Szpital Kliniczny Klinika

Wroclaw, 50-367, Poland

Location

Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"

Omsk, Omsk Oblast, 644013, Russia

Location

Federal State Budgetary Institution "Russian Scientific and Research Institute of Hematology and Transfusiology of Federal Medico-Biological Agency

Saint Petersburg, 191024, Russia

Location

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

Saint Petersburg, 197022, Russia

Location

Oncology Dispensary #2 of Krasnodar Region

Sochi, 354057, Russia

Location

Gleneagles Medical Centre

Singapore, Central Singapore, 258499, Singapore

Location

Gachon University Gil Hospital

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

Location

Pusan National University Hospital

Busan, Pusan-Kwangyǒkshi, 49241, 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

Inje Univ Busan Paik Hospital

Busan, 47392, South Korea

Location

Hospital Duran I Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario de Toledo

Toledo, Castille-La Mancha, 45004, Spain

Location

Complejo Hospitalario Universitario de Santiago de Compostel

Santiago de Compostela, La Coruna, 15706, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Planta Baja, 28007, Spain

Location

Hospital General de Albacete

Albacete, 02006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitario Infanta Leonor-INTERNAL MED

Madrid, 28031, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Marques De Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario de Alava

Vitoria-Gasteiz, 01005, Spain

Location

Clinica di Ematologia IOSI, Ospedale Bellinzona e Valli, Ente Ospedaliero Cantonale

Bellinzona, Svizzera, 6500, Switzerland

Location

China Medical University Hospital

Taichung, Taichung, 40447, Taiwan

Location

Tri-Service General Hospital

Taipei City, Taipei, 114, Taiwan

Location

Chang Gung Memorial Hospital - Linkou

Taoyuan, (r.o.c.), Taiwan, 33342, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

Location

Ankara University Medicine Hospital

Mamak, Ankara, Turkey (Türkiye)

Location

Istanbul University Istanbul Medicine Faculty

Faith, Istanbul, Turkey (Türkiye)

Location

Erciyes University Faculty of Medicine

Kayseri, Melikgazi, 38039, Turkey (Türkiye)

Location

Gazi University Faculty of Medicine

Ankara, Yenimahalle, 06560, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Dokuz Eylul University Faculty of Medicine

Izmir, 35330, Turkey (Türkiye)

Location

Aberdeen Royal Infirmary

Aberdeen, Aberdeen City, AB25 2ZN, United Kingdom

Location

The Royal Cornwall Hospital

Truro, Cornwall, TR1 3LJ, United Kingdom

Location

Derriford Hospital

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Castle Hill Hospital

Cottingham, East Yorkshire, HU16 5JQ, United Kingdom

Location

University College London Hospitals

London, Greater London, WC1E 6HX, United Kingdom

Location

Norfolk and Norwich Hospital

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

Singleton Hospital

Swansea, SA2 8QA, United Kingdom

Location

Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

St Johns Hospital at Howden

Livingston, West Lothian, EH54 6PP, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Milton Keynes University Hospital

Milton Keynes, MK6 5LD, United Kingdom

Location

GenesisCare Cambridge

Newmarket, CB8 7XN, United Kingdom

Location

Related Publications (1)

• Sharman JP, Munir T, Grosicki S, Roeker LE, Burke JM, Chen CI, Grzasko N, Follows G, Matrai Z, Sanna A, Qiu L, Feng R, Hua VM, Jurczak W, Ritgen M, Yi S, Bosch F, Coombs CC, Bao K, Patel V, Liu B, Compte L, Guntur A, Wang DY, Hill M, Leow CC, Ghia P, Barr PM. Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321). J Clin Oncol. 2025 Aug;43(22):2538-2549. doi: 10.1200/JCO-25-00166. Epub 2025 Jun 6.

  PMID: 40479620 DERIVED

MeSH Terms

Conditions

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

Interventions

pirtobrutinib; idelalisib; 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

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Marisa Hill, MD

  Loxo Oncology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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 in 1:1 into Arm A or 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. Patients who discontinue treatment for toxicity may still be evaluated for cross over at the time of IRC-confirmed PD.

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: March 9, 2021
• Primary Completion: August 29, 2023
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 24, 2026
• Results First Posted: March 7, 2025

Record last verified: 2026-04

Locations

HU (4); AU (3); CN (20); BE (7); JP (18); PL (13); KR (6); IT (25); CH (1); IL (5); TU (6); CZ (3); SG (1); DE (8); FR (14); CA (4); IE (3); TW (4); US (46); GB (13); CR (2); RU (4); ES (15)