Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)

Lymphoma, Mantle-Cell Clinical Trial

— BRUIN-MCL-321  

Official title:

A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04662255
• Other study ID #: LOXO-BTK-20019
• Secondary ID: J2N-OX-JZNM
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 8, 2021
• Est. completion date: July 2026

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two years, and possibly longer, if the disease does not progress.

Description:

This is a Phase 3 global, randomized, open-label study comparing pirtobrutinib (Arm A) to investigator's choice of ibrutinib, acalabrutinib or zanubrutinib (Arm B) in MCL patients who have received 1 or more lines of therapy and are BTK inhibitor naïve.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: July 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed MCL diagnosis

• Previously treated with at least one prior line of systemic therapy for MCL

• Measurable disease per Lugano criteria

• Eastern Cooperative Oncology Group (ECOG) 0-2

• Absolute neutrophil count = 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening

• Hemoglobin = 8 g/dL not requiring transfusion support or growth factors within 7 days of screening

• Platelets = 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening.

• AST and ALT = 3.0 x upper limit of normal (ULN)

• Total bilirubin = 1.5 x ULN.

• Creatinine clearance of = 30 mL/min according to Cockcroft/Gault Formula

Exclusion Criteria:

• Prior treatment with an approved or investigational BTK inhibitor

• History of bleeding diathesis

• History of stroke or intracranial hemorrhage within 6 months of randomization

• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization

• Clinically significant cardiovascular disease

• Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3 consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs

• Known HIV infection or active HBV, HCV, or CMV infections. (Certain participants with controlled HBV infections may still be eligible)

• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption

• Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.

• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.

• Vaccination with live vaccine within 28 days prior to randomization

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• Pirtobrutinib
Oral
• Ibrutinib
Oral
• Acalabrutinib
Oral
• Zanubrutinib
Oral

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Icon Cancer Care - The Wesley Medical Centre	Auchenflower
Australia	Andrew Lowe Cancer Centre	Geelong	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	The St. George Hospital	Kogarah	New South Wales
Australia	Linear Clinical Research Ltd	Nedlands	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz	Oberösterreich
Austria	Uniklinikum Salzburg	Salzburg	Osterreich
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Belgium	AZ Delta	Roeselare
Brazil	HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas	Campinas	Sao Paulo
Brazil	HC-UFPR- Hospital de Clinicas da Universidade Federal do Parana	Curitiba	Paraná
Brazil	NOHC- Nucleo de Oncologia e Hematologia do Ceara e Oncovie	Fortaleza	Ceará
Brazil	HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás	Goiânia	Goiás
Brazil	Hospital Sao Lucas Copacabana	Rio de Janeiro
Brazil	INCA - Instituto Nacional de Cancer	Rio De Janeiro
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo Andre	Sao Paulo
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	São José Do Rio Preto	São Paulo
Brazil	Hospital Sao Domingos	São Luís	Maranhão
Brazil	IEP - Instituto de Ensino e Pesquisas São Lucas	Sao Paulo
Brazil	A. C. Camargo Cancer Center	São Paulo
Brazil	Albert Einstein Sociedade Beneficente Israelita Brasileira	São Paulo
Brazil	BP A Beneficencia Portuguesa da Sao Paulo	São Paulo
Brazil	HC-FMUSP	São Paulo
Brazil	Hospital Nove de Julho	São Paulo
Brazil	Irmandade da Santa Casa de Misericordia de Sao Paulo	São Paulo
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer Vancouver	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
China	Beijing Chaoyang Hospital, Capital Medical University	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Beijing Cancer hospital	Haidian District	Beijing
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Anhui Provincial Cancer Hospital	Hefei	Anhui
China	Lishui Municipal Central Hospital	Lishui	Zhejiang
China	The First Affiliated Hospital of Henan Science and Technology University	Luoyang	Henan
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Blood Institute of the Chinese Academy of Medical science	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Affiliated Tumor Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Wuhan Union Hospital	Wuhan	Hubei
China	Yichang Central People's Hospital	Yichang	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Denmark	Aarhus Universitetshospital, Aarhus Sygehus	Aarhus N	Jutland
Denmark	Odense Universitetshospital	Odense
France	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux	Aquitaine
France	Hopital Saint Vincent De Paul	Lille cedex
France	Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu	Nantes Cedex 1
France	Groupe Hospitalier Pitie-Salpetriere	Paris
France	Centre hospitalier universitaire de Haut Leveque	Pessac Cedex
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex
France	Pole Regionalde Cancérologie(CHU de Poitiers)	Politiers
France	Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen	Rouen	Seine-Maritime
France	Institut Curie	Saint-Cloud	Île-de-France
France	CHRU De Tours	Tours	Tours Cedex 9
France	Chu De Nancy Hop D'Adultes De Brabois	Vandœuvre-lès-Nancy
Germany	OncoResearch Lerchenfeld GmbH	Hamburg
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Kiel	Kiel	Schleswig Holstein
Germany	InVO - Institut für Versorgungsforschung in der Onkologie GbR	Koblenz	Rhineland-Palatinate
Germany	Universitätsmedizin Johannes Gutenberg Universität Mainz	Mainz
Germany	Klinikum der Universität München Großhadern	München	Bayern
Germany	Universitaetsklinikum Muenster	Munster
Germany	Universitaetsklinikum Muenster	Münster	Nordrhein-Westfalen
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Hungary	Debreceni Egyetem	Debrecen
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont	Pécs	Baranya
Ireland	St James's Hosptial	Dublin	Dublin 8
Israel	Bnai Zion Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Presidio Ospedaliero Civile Santi Antonio e Biagio	Alessandria	AL
Italy	IRCCS - AOU di Bologna	Bologna
Italy	IRCCS Ospedale Policlinico San Martino	Genova
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola	Emilia-Romagna
Italy	Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte	Messina
Italy	Ospedale San Raffaele	Milano	Lombardia
Italy	Ospedale Vincenzo Cervello	Palermo
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Irccs Crob	Rionero in Vulture	Potenza
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti	Torrette	Ancona
Italy	Ospedale di Circolo e Fondazione Macchi Varese	Varese
Italy	Irccs Istituto Tumori Giovanni Paolo Ii	Viale Orazio Flacco	Bari
Japan	Chugoku Central Hospital	Hiroshima
Japan	Saitama Medical Center	Kawagoe	Saitama
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Japanese Foundation for Cancer Research	Koto	Tokyo
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kyoto Furitsu Medical University Hospital	Kyoto-shi
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Nagoya Medical Center	Nagoya	Aichi
Japan	Kochi Medical School Hospital	Nankoku	Kochi
Japan	Okayama University Hospital	Okayama
Japan	Kindai University Hospital	Osaka Sayama-shi	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tohoku University Hospital	Sendai-shi	Miyagi
Japan	NTT Medical Center Tokyo	Shinagawa-KU	Tokyo
Korea, Republic of	Inje Univ Busan Paik Hospital	Busan
Korea, Republic of	Kosin University Gospel Hospital	Busan	Seogu
Korea, Republic of	Gachon University Gil Hospital	Namdong-gu	Incheon-gwangyeoksi [Incheon]
Korea, Republic of	The Catholic University of Korea-Seoul St. Mary's Hospital	Seocho-Gu	Seoul
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul, Korea
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [Seoul]
Netherlands	Ziekenhuisapotheek HagaZiekenhuis	Den Haag
Netherlands	Bravis Ziekenhuis	Roosendaal
Netherlands	Erasmus Medisch Centrum	Rotterdam
Netherlands	Spaarne Gasthuis	TM Hoofddorp
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Middlemore Clinical Trials	Papatoetoe	Auckland
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Pratia MCM Krakow	Krakow
Poland	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii	Lódz
Poland	Centrum Onkologii Ziemi Lubelskiej	Lublin	Lubelskie
Poland	Centrum Medyczne Pratia Poznan	Skórzewo
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Portugal	Champalimaud Foundation	Lisboa
Portugal	IPOFG - Lisboa	Lisboa
Russian Federation	GUZ of Moscow City Clinical Hospital n.a. S.P. Botkin	Moscow
Russian Federation	Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"	Omsk	Omskaya Oblast'
Russian Federation	Federal State Budgetary Institution "Russian Scientific and Research Institute of Hematology and Transfusiology of Federal Medico-Biological Agency	Saint Petersburg
Russian Federation	State Medical University named after I.P. Pavlov	Saint-Petersburg
Spain	Complejo Hospitalario Universitario de Santiago	A Coruña
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Duran I Reynals	Hospitalet De Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Infanta Leonor	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga	Andalucia
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Switzerland	Ospedale Regionale Bellinzona e Valli	Bellinzona
Switzerland	Kantonsspital Luzern	Luzern 16	Luzern
Taiwan	Chang Gung Memorial Hospital - Chiayi	Chiayi County
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei City	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan City
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Aberdeen City
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Stratchclyde
United Kingdom	Churchill Hospital	Headington	Oxford
United Kingdom	GenesisCare Cambridge	Newmarket
United Kingdom	City Hospital, Nottingham University Hospitals	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United Kingdom	GenesisCare, Windsor	Windsor
United Kingdom	New Cross Hospital	Wolverhampton
United States	Alaska Oncology & Hematology, LLC	Anchorage	Alaska
United States	University of Michigan	Ann Arbor	Michigan
United States	Messino Cancer Center	Asheville	North Carolina
United States	Rocky Mountain Cancer Center	Aurora	Colorado
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	Texas Oncology - Bedford	Bedford	Texas
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Willamette Valley Cancer Institute & Research Ctr.	Eugene	Oregon
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	St. Joseph Heritage Healthcare	Fullerton	California
United States	Virginia Cancer Specialists, PC	Gainesville	Virginia
United States	Texas Oncology - Bayler Charles A. Sammons Cancer Center	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC	Kansas City	Missouri
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of Kentucky Markey Cancer Center	Lexington	Kentucky
United States	The Oncology Institute of Hope and Innovation	Long Beach	California
United States	UCLA Medical Center	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Texas Oncology - McAllen	McAllen	Texas
United States	Texas Oncology - McKinney	McKinney	Texas
United States	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	Hematology Oncology Associates Of Northern New Jersey	Morristown	New Jersey
United States	Sarah Cannon Research Institute SCRI	Nashville	Tennessee
United States	Cancer Center Office of Clinical Research	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Medical College	New York	New York
United States	Medical Oncology Hematology Consultants, PA	Newark	Delaware
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Mercy Health-Paducah Medical Oncology and Hematology	Paducah	Kentucky
United States	Arizona Oncology Associates, P.C. - HOPE	Phoenix	Arizona
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University Medical School	Saint Louis	Missouri
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Oregon Oncology Specialists	Salem	Oregon
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Texas Oncology - Sherman	Sherman	Texas
United States	Florida Cancer Specialists	Tallahassee	Florida
United States	Oncology-Hematology Associates of West Broward	Tamarac	Florida
United States	Arizona Oncology Associates, P.C. - HOPE	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Florida Cancer Specialists East	West Palm Beach	Florida
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Loxo Oncology, Inc.	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Portugal,  Russian Federation,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL)	Assessed per Lugano criteria	Up to approximately 24 months
Secondary	To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms	Defined as the time from randomization to progressive disease (PD) or start of new treatment for MCL or withdrawal from trial due to toxicity or death	Up to approximately 24 months
Secondary	To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms	Time from randomization to time when discontinuation criteria met	Up to approximately 24 months
Secondary	Time to worsening (TTW) of MCL-related symptoms	Using symptom questions identified from the European Organization for Research and Treatment of Cancer (EORTC) item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.	Up to approximately 24 months
Secondary	Comparative Tolerability as measured by proportion of time with high side effect burden	Using 18 items covering 10 Patient Reported Outcome- Common Terminology Criteria for Adverse Events (PRO-CTCAE) concepts for frequency (0-5 with 5 as most frequent), and/or presence (0-1 with 1 being present), or Severity (0-5 with 5 as most severe) and/or presence (0-1 with 1 being present); these selective adverse events will be framed and then overall side effect burden will be ascertained with the Functional Assessment of Cancer Therapy (FACT) - Item GP5. The range of this item is 0 -4 with 4 as most bothersome.	Up to approximately 24 months
Secondary	To compare Overall Response Rate (ORR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms	Assessed per Lugano criteria	Up to approximately 24 months
Secondary	To compare Duration of Response (DOR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms	Assessed per Lugano criteria	Up to approximately 24 months
Secondary	To compare Overall Survival of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms	Assessed by survival	Up to approximately 24 months