Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)
- Conditions
- Lymphoma, Mantle-Cell
- Interventions
- Registration Number
- NCT04662255
- Lead Sponsor
- Loxo Oncology, Inc.
- Brief 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.
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib) Ibrutinib Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country. Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib) Acalabrutinib Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country. Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib) Zanubrutinib Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country. Arm A (Pirtobrutinib) Pirtobrutinib Orally
- Primary Outcome Measures
Name Time Method 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) Up to approximately 24 months Assessed per Lugano criteria
- Secondary Outcome Measures
Name Time Method To compare Overall Response Rate (ORR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms Up to approximately 24 months Assessed per Lugano criteria
To compare Overall Survival of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms Up to approximately 24 months Assessed by survival
To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms Up to approximately 24 months 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
To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms Up to approximately 24 months Time from randomization to time when discontinuation criteria met
Time to worsening (TTW) of MCL-related symptoms Up to approximately 24 months 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.
Comparative Tolerability as measured by proportion of time with high side effect burden Up to approximately 24 months 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.
To compare Duration of Response (DOR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms Up to approximately 24 months Assessed per Lugano criteria
Trial Locations
- Locations (189)
Alaska Oncology and Hematology, LLC
🇺🇸Anchorage, Alaska, United States
Arizona Oncology Associates, P.C. - HOPE
🇺🇸Phoenix, Arizona, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
USO-Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Oncology-Hematology Associates of West Broward
🇺🇸Tamarac, Florida, United States
Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
University of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Mercy Health-Paducah Medical Oncology and Hematology
🇺🇸Paducah, Kentucky, United States
Tulane Cancer Center Office of Clinical Research
🇺🇸New Orleans, Louisiana, United States
Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
DFCI Lymphoma
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University Medical School
🇺🇸Saint Louis, Missouri, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Messino Cancer Center
🇺🇸Asheville, North Carolina, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Wake Forest University School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, United States
Willamette Valley Cancer Institute & Research Ctr.
🇺🇸Eugene, Oregon, United States
Sarah Cannon Research Institute SCRI
🇺🇸Nashville, Tennessee, United States
Texas Oncology-Austin Midtown
🇺🇸Austin, Texas, United States
Texas Oncology - Bedford
🇺🇸Bedford, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Oncology - McAllen
🇺🇸McAllen, Texas, United States
Texas Oncology - Sherman
🇺🇸Sherman, Texas, United States
US Oncology
🇺🇸The Woodlands, Texas, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
USO-Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Froedtert Memorial Lutheran Hospital
🇺🇸Milwaukee, Wisconsin, United States
The St. George Hospital
🇦🇺Kogarah, New South Wales, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Icon Cancer Care - The Wesley Medical Centre
🇦🇺Auchenflower, Australia
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Oberösterreich, Austria
Uniklinikum Salzburg
🇦🇹Salzburg, Osterreich, Austria
Universitair Ziekenhuis Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
AZ Delta
🇧🇪Roeselare, West Flanders, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Hospital São Lucas Copacabana
🇧🇷Rio de Janeiro, CEP, Brazil
Hospital Beneficência Portuguesa de São Paulo
🇧🇷São Paulo, CEP, Brazil
Centro de Oncologia e Hematologia do Ceará LTDA
🇧🇷Aldeota, Fortaliza, Brazil
Hospital das Clínicas da UFGo - Goiânia
🇧🇷Goiânia, Goiás, Brazil
Hospital Sao Domingos
🇧🇷São Luís, MA, Brazil
Instituto Nacional de Câncer - INCA
🇧🇷Rio de Janeiro, Rio De Jan, Brazil
Centro de Pesquisa Clínica São Lucas
🇧🇷Campinas, Sau Paulo, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto, Dept. CIP - Centro Integrado de Pesquisa
🇧🇷Rio Preto, SP, Brazil
Instituto de Ensino e Pesquisas São Lucas - IEP Hemomed
🇧🇷Pacaembu, São Paulo, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
🇧🇷Santo André, São Paulo, Brazil
A. C. Camargo Cancer Center
🇧🇷Sao Paulo, São Paulo, Brazil
HC - UFPR - Hospital de Clínicas da Universidade Federal do Paraná
🇧🇷Curitiba- PR, Brazil
Hospital da Clinicas da Faculdade de Medicina da USP
🇧🇷Sao Paulo, Brazil
Hospital 9 De Julho
🇧🇷Sao Paulo, Brazil
IPITEC
🇧🇷São Paulo, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
🇧🇷São Paulo, Brazil
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
BC Cancer Vancouver
🇨🇦Vancouver, British Columbia, Canada
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Anhui Provincial Cancer Hospital
🇨🇳Hefei, Anhui, China
Beijing ChaoYang Hospital
🇨🇳Beijing, Beijing, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
Beijing Cancer hospital
🇨🇳Beijing, Beijing, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Fujian Provincial Cancer Hospial
🇨🇳Fuzhou, Fujian, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Southern Medical University Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Henan University of Science &Technology
🇨🇳Luoyang, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Wuhan Union Hospital
🇨🇳Wuhan, Hubei, China
Yichang Central People's Hospital
🇨🇳Yichang, Hubei, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University
🇨🇳Cheng Du, Sichuan, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Affiliated Tumor Hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Lishui Central Hospital
🇨🇳Lishui, Zhejiang, China
Chongqing Cancer Hospital
🇨🇳Chongqing, China
Blood Institute of the Chinese Academy of Medical science
🇨🇳Tianjin, China
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Hradec Králové, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Aarhus Universitetshospital, Aarhus Sygehus
🇩🇰Aarhus N, Jutland, Denmark
Odense Universitetshospital
🇩🇰Odense C, Syd, Denmark
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
🇫🇷Bordeaux, Aquitaine, France
Hopital de la Pitie Salpetriere
🇫🇷Paris, Cedex 13, France
Chu De Nancy Hop D'Adultes De Brabois
🇫🇷Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France
Hôpital Saint Vincent-de-Paul
🇫🇷Lille, Nord-Pas-de-Calais, France
Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen
🇫🇷Rouen, Seine-Maritime, France
Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
🇫🇷Nantes, France
Institut Curie
🇫🇷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
CHRU De Tours
🇫🇷Tours Cedex, France
Universitätsklinikum Ulm
🇩🇪Ulm, Baden-Württemberg, Germany
Klinikum der Universität München Großhadern
🇩🇪Würzburg, Bayern, Germany
Universitätsklinikum Gießen und Marburg GmbH
🇩🇪Gießen, Hessen, Germany
Universitätsklinikum Münster - Albert Schweitzer Campus
🇩🇪Münster, Nordrhein-Westfalen, Germany
InVO Institut für Versorgungsforschung in der Onkologie
🇩🇪Koblenz, Rheinland-Pfalz, Germany
Universitätsmedizin Johannes Gutenberg Universität Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Schleswig-Holstein, Germany
OncoResearch Lerchenfeld GmbH
🇩🇪Hamburg, Germany
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, Israel
Presidio Ospedaliero Civile Santi Antonio e Biagio
🇮🇹Alessandria, AL, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Emilia-Romagna, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Emilia-Romagna, Italy
Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
IRCCS - AOU di Bologna
🇮🇹Bologna, Italy
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Ospedale Vincenzo Cervello
🇮🇹Palermo, Italy
Irccs Crob
🇮🇹Potenza, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Ospedale Di Circolo E Fondazione Macchi
🇮🇹Varese, Italy
Nagoya Medical Center
🇯🇵Nagoya, Aichi, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Aichi, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Hyogo, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Miyagi, Japan
Kindai University Hospital
🇯🇵Osaka Sayama-shi, Osaka, Japan
Saitama Medical Center
🇯🇵Kawagoe, Saitama, Japan
Japanese Foundation for Cancer Research
🇯🇵Koto, Tokyo, Japan
Chugoku Central Hospital
🇯🇵Hiroshima, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Kyoto Furitsu Medical University Hospital
🇯🇵Kyoto, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Gachon University Gil Medical Center
🇰🇷Namdong-gu, Incheon-gwangyeoksi [Incheon], Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Korea, Republic of
Kosin University Gospel Hospital
🇰🇷Busan, Seogu, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Bravis Ziekenhuis
🇳🇱Bergen op Zoom, Noord-Brabant, Netherlands
Ziekenhuisapotheek HagaZiekenhuis
🇳🇱Den Haag, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Christchurch Hospital
🇳🇿Addington, Christchurch, New Zealand
Middlemore Clinical Trials
🇳🇿Auckland, New Zealand
Centrum Onkologii Ziemi Lubelskiej
🇵🇱Lublin, Lubelskie, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Pratia MCM Krakow
🇵🇱Krakow, Poland
AIDPORT Sp. z o.o.
🇵🇱Skorzewo, Poland
Uniwersytecki Szpital Kliniczny Klinika
🇵🇱Wrocław, Poland
Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii
🇵🇱Łódź, Poland
IPOFG - Lisboa
🇵🇹Lisboa, Portugal
Champalimaud Foundation
🇵🇹Lisboa, Portugal
GUZ of Moscow City Clinical Hospital n.a. S.P. Botkin
🇷🇺Moscow, Russian Federation
Fed. State Budgetary Institution "Russian Scientific & Research Institute of Hemat. & Transfusiology of Fed. Medico-Bio. Agency
🇷🇺Saint Petersburg, Russian Federation
State Medical University named after I.P. Pavlov
🇷🇺Saint-Petersburg, Russian Federation
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Andalucía, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Hospital Duran I Reynals
🇪🇸Hospitalet De Llobregat, Barcelona, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Palma De Mallorca(Baleares), Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Kantonsspital Luzern
🇨🇭Luzern 16, Luzern, Switzerland
Tri-Service General Hospital
🇨🇳Taipei City, Taipei, 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 Uni. Hosp.
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital - Linkou
🇨🇳Taoyuan City, Taiwan
Aberdeen Royal Infirmary
🇬🇧Aberdeen, Aberdeen City, United Kingdom
Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
GenesisCare
🇬🇧Newmarket, Suffolk, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
City Hospital, Nottingham University Hospitals
🇬🇧Nottingham, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
GenesisCare, Windsor
🇬🇧Windsor, United Kingdom