Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
LOTIS 5
A Phase 3 Randomized Study of Loncastuximab Tesirine Combined With Rituximab Versus Immunochemotherapy in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-5)
2 other identifiers
interventional
440
21 countries
144
Brief Summary
The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2020
Longer than P75 for phase_3
144 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 8, 2020
CompletedFirst Posted
Study publicly available on registry
May 12, 2020
CompletedStudy Start
First participant enrolled
September 16, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2028
ExpectedApril 28, 2026
April 1, 2026
5.5 years
May 8, 2020
April 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS)
Up to 4 years
Secondary Outcomes (18)
Overall Survival (OS)
Up to 4 years
Overall Response Rate (ORR)
Up to 4 years
Complete Response Rate (CRR)
Up to 4 years
Duration of Response (DOR)
Up to 4 years
Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE)
Day 1 up to a maximum of Week 39
- +13 more secondary outcomes
Study Arms (3)
Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R)
EXPERIMENTALPart 1 consists of a non-randomized safety run-in period evaluating the study drug for the first 20 participants. Participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m\^2 Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m\^2 Q3W for up to 6 additional cycles.
Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R)
EXPERIMENTALRandomized participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m\^2 every Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m\^2 Q3W for up to 6 additional cycles.
Part 2: Standard Immunochemotherapy (R-GemOx)
ACTIVE COMPARATORRandomized participants will receive R-GemOx consisting of rituximab, gemcitabine and oxaliplatin as a standard immunochemotherapy treatment on Day 1 or Day 2 of each cycle for up to 8 cycles, where 1 Cycle is 2 weeks. R-GemOx will be administered via an intravenous infusion of rituximab 375 mg/m\^2 + gemcitabine 1000 mg/m\^2 + oxaliplatin 100 mg/m\^2 every 2 weeks (Q2W) for up to 8 cycles.
Interventions
Intravenous Infusion
Intravenous Infusion
Eligibility Criteria
You may qualify if:
- Male or female participant aged 18 years or older
- Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization classification (including participants with DLBCL transformed from indolent lymphoma), or high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
- Relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) disease following at least one multi-agent systemic treatment regimen \[For China only: Adequate first line anti-DLBCL therapy is defined as having received at least 4 cycles of multiagent systemic treatment regimen containing rituximab and anthracycline, unless the participants are intolerant to the regimen, or had disease progression during the treatment. If disease progression occurred during the treatment period, then the disease is considered refractory where the number of treatment cycles will not be specified. For participants who are ineligible for anthracycline, anthracycline is not required.\]
- Not considered by the investigator to be a candidate for stem cell transplantation based on performance status, advanced age, and/or significant medical comorbidities such as organ dysfunction
- Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if tumor is not fluorodeoxyglucose (FDG)-avid on screening PET-CT
- ECOG performance status 0-2
- Adequate organ function as defined by screening laboratory values within the following parameters:
- Absolute neutrophil count ≥1000/μL (off growth factors for at least 72 hours)
- Platelet count ≥100000/μL without transfusion within the past 2 weeks
- ALT, AST, and GGT ≤2.5 × the upper limit of normal (ULN)
- Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
- Calculated creatinine clearance ≥30 mL/min by the Cockcroft and Gault equation
- Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility.
- Negative beta-human chorionic gonadotropin (β-hCG) pregnancy test within 7 days prior to start of study drug (Cycle 1 Day 1) for women of childbearing potential
- Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 12 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 7 months after the participant receives his last dose of study treatment.
You may not qualify if:
- Previous treatment with loncastuximab tesirine
- Previous treatment with R-GemOx
- Known history of hypersensitivity to a CD19 antibody, loncastumiximab tesirine (including SG3249) or any of its excipients, or history of positive serum human ADA to a CD19 antibody
- Pathologic diagnosis of Burkitt lymphoma
- Autologous transplant within 30 days prior to start of study drug (Cycle 1 Day 1)
- Allogeneic transplant within 60 days prior to start of study drug (Cycle 1 Day 1)
- Active graft-versus-host disease
- Post-transplantation lymphoproliferative disorders
- Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
- Human immunodeficiency virus (HIV) seropositive with any of the following:
- CD4+ T-cell (CD4+) counts \<350 cells/μL
- Acquired immunodeficiency syndrome-defining opportunistic infection within 12 months prior to screening
- Not on anti-retroviral therapy, or on anti-retroviral therapy for \<4 weeks at the time of screening
- HIV viral load ≥400 copies/mL
- Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (144)
University of California San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Redlands Community Hospital
Redlands, California, 92373, United States
The Oncology Institute of Hope and Innovation
Whittier, California, 90603, United States
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207, United States
UnityPoint Health - Iowa Oncology Research Association (IORA)
Des Moines, Iowa, 50309, United States
Norton Cancer Institute
Louisville, Kentucky, 40207, United States
Comprehensive Cancer Centers of Nevada - Henderson
Las Vegas, Nevada, 89169, United States
Kaiser Permanente Interstate Medical Office Central
Portland, Oregon, 97227, United States
Hollings Cancer Center
Charleston, South Carolina, 29425, United States
Virginia Cancer Specialists
Gainesville, Virginia, 20155, United States
Medical College of Wisconsin Cancer Center Clinical Trials Office
Milwaukee, Wisconsin, 53226, United States
Clinica Adventista Belgrano
Belgrano, Buenos Aires, C1430EGF, Argentina
Clínica de Nefrología, Urología y Enfermedades Cardiovasculares S.A.
Santa Fe, Buenos Aires, 3000, Argentina
Instituto Médico Especializado Alexander Fleming
Buenos Aires, Distrito Federal, C1426ANZ, Argentina
Grupo Gamma - Hospital Privado Rosario
Rosario, Santa Fe Province, S2000GAP, Argentina
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
Bruges, 8000, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
Centre Hospitalier Universitaire Universite Catholique de Louvain
Namur, B-5530, Belgium
Algemeen Ziekenhuis Delta - Campus Rumbeke
Roeselare, 8800, Belgium
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, Paraná, 81520-060, Brazil
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-001, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Hospital Mãe de Deus - Centro Integrado de Oncologia
Porto Alegre, Rio Grande do Sul, 90110-270, Brazil
Hospital do Câncer
Rio de Janeiro, 20230-130, Brazil
Hemomed Instituto de Oncologia e Hematologia
São Paulo, 01236-030, Brazil
A Beneficência Portuguesa de São Paulo - Unidade Mirante
São Paulo, 01321-001, Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, 05403-010, Brazil
Hospital Israelita Albert Einstein
São Paulo, 05652-900, Brazil
Hospital Santa Marcelina
São Paulo, 08270-120, Brazil
Cross Cancer Institute
Edmonton, T6G 1Z2, Canada
Research Institute of the McGill University Health Centre
Montreal, H4A 3J1, Canada
Hôpital Fleurimont
Sherbrooke, J1H 5H3, Canada
Centro de Estudios Clínicos SAGA
Santiago, Santiago Metropolitan, 7500653, Chile
Instituto Oncológico Fundación Arturo López Pérez
Santiago, Santiago Metropolitan, 8320000, Chile
CeCim - Centro de Estudios Clínicos e Investigaciones Médicas
Santiago, Santiago Metropolitan, 8330109, Chile
Peking University Third Hospital
Beijing, Beijing Municipality, 100191, China
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361001, China
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510060, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080, China
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510280, China
Henan Cancer Hospital - Zhengzhou University
Zhengzhou, Henan, 450008, China
Jilin Cancer Hospital
Changchun, Jilin, 130021, China
The First Hospital of Jilin University
Changchun, Jilin, 130021, China
Second Affiliated Hospital of Dalian Medical University
Dalian, Liaoning, 116000, China
Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200025, China
West China School of Medicine - West China Hospital of Sichuan University
Chengdu, Sichuan, 610041, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality, 300060, China
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Chongqing University Cancer Hospital - Chongqing Cancer Hospital
Chongqing, 400030, China
Huizhou Municipal Central Hospital
Huizhou, 516001, China
The First Affiliated Hospital of Nanchang University
Nanchang, 330006, China
Institute of Hematology and Blood Diseases Hospital of CAMS - PUMC
Tianjin, 300020, China
Wuhan Union Hospital
Wuhan, 430023, China
Tongji Hospital
Wuhan, 430030, China
Fakultni nemocnice Ostrava
Ostrava, 708 52, Czechia
Fakultni Nemocnice Kralovske Vinohrady
Prague, 100 34, Czechia
Fakultni nemocnice v Motole
Prague, 150 06, Czechia
Centre Hospitalier Regional Universitaire Brest
Brest, Brittany Region, 29200, France
Hôpital Avicenne
Bobigny, 93000, France
Centre Hospitalier Regional Universitaire Brest
Brest, 29200, France
Hôpital François Mitterrand
Dijon, 21000, France
Hôpital Privé du Confluent
Nantes, 44200, France
Hopital Universitaire Pitie Salpetriere
Paris, 75651, France
Hôpital Haut-Lévêque
Pessac, 33604, France
Centre de Lutte Contre le Cancer - Centre Henri-Becquerel
Rouen, 76038, France
Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet
Heves, Budapest, 3300, Hungary
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet - Szent László
Budapest, Pest County, 1097, Hungary
Semmelweis Egyetem
Budapest, 1088, Hungary
Orszagos Onkologiai Intezet
Budapest, 1122, Hungary
Samson Assuta Ashdod University Hospital
Ashdod, 7747629, Israel
Soroka Medical Center
Beersheba, 8410101, Israel
Shamir Medical Center (Assaf Harofeh)
Be’er Ya‘aqov, 7030000, Israel
Carmel Medical Center
Haifa, 3436212, Israel
Rabin Medical Center - Beilinson Hospital
Petah Tikva, 4941492, Israel
The Chaim Sheba Medical Center
Tel Aviv, 52621, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Presidio Ospedaliero Universitario Santa Maria della Misericordia
Udine, Friuli Venezia Giulia, 33100, Italy
Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia
Brescia, 25123, Italy
Azienda Ospedaliero - Universitaria Careggi
Florence, 50134, Italy
Ospedale Casa Sollievo della Sofferenza
Foggia, 71013, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
Meldola, 47014, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
Milan, 20089, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
Milan, 20132, Italy
Istituto Europeo di Oncologia
Milan, 20141, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100, Italy
Sanitaria Locale della Romagna
Ravenna, 48121, Italy
National Hospital Organization - Nagoya Medical Center
Nagoya, Aichi-ken, 460-0001, Japan
Toyohashi Municipal Hospital
Toyohashi, Aichi-ken, 441-8570, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577, Japan
Matsuyama Red Cross Hospital
Matsuyama, Ehime, 790-8524, Japan
Gunma Prefectural Cancer Center
Ōta, Gunma, 373-8550, Japan
Sapporo Hokuyu Hospital
Sapporo, Hokkaido, 003-0006, Japan
Hokkaido Cancer Center
Sapporo, Hokkaido, 003-0804, Japan
Kobe City Medical Center General Hospital
Kobe, Hyōgo, 650-0047, Japan
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515, Japan
Tohoku University Hospital
Sendai, Miyagi, 980-8574, Japan
Nagasaki University Hospital
Nagasaki, Nagasaki, 852-8501, Japan
Saitama Medical University - International Medical Center
Hidaka-Shi, Saitama, 350-1298, Japan
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Bunkyo-ku, Tokyo, 113-8677, Japan
National Hospital Organization Disaster Medical Center
Tachikawa, Tokyo, 190-0014, Japan
Fukushima Medical University Hospital
Fukushima, 960-1295, Japan
Gifu Municipal Hospital
Gifu, 500-8323, Japan
Kagoshima University Hospital
Kagoshima, 890-8520, Japan
Niigata University Medical and Dental Hospital
Niigata, 951-8520, Japan
National Hospital Organization Okayama Medical Center
Okayama, 701-1192, Japan
Osaka Prefectural Hospital Organization - Osaka International Cancer Institute
Osaka, 541-8567, Japan
Boca Raton Clinical Research (BRCR) Global Mexico - Guadalajara
Guadalajara, Jalisco, 44600, Mexico
PanAmerican Clinical Research Mexico - Guadalajara
Guadalajara, Jalisco, 44670, Mexico
PanAmerican Clinical Research Mexico - Cuernavaca
Cuernavaca, Morelos, 62290, Mexico
Hospital Universitario Dr. José Eleuterio González
Monterrey, Nuevo León, 64460, Mexico
Hematológica Alta Especialidad
Huixquilucan, 52787, Mexico
Boca Raton Clinical Research (BRCR) Global Mexico - Ciudad de México
Mexico City, 1120, Mexico
Hagaziekenhuis Van Den Haag - Leyweg
The Hague, South Holland, 2545 AA, Netherlands
Elisabeth-TweeSteden Ziekenhuis - Elisabeth
Tilburg, 5022 GC, Netherlands
Pratia MCM Kraków
Krakow, Lesser Poland Voivodeship, 30-510, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
Wroclaw, Lower Silesian Voivodeship, 50-367, Poland
Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością
Gdynia, 81-519, Poland
Pratia Onkologia Katowice
Katowice, 40-519, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz, 93-510, Poland
Szpital Wojewódzki w Opolu
Opole, 45-061, Poland
Centrum Medyczne Pratia Poznań
Skorzewo, 60-185, Poland
Instytut Hematologii I Transfuzjologii
Warsaw, 02-776, Poland
Hospital Español Auxilio Mutuo
San Juan, 00919, Puerto Rico
Hospital del Mar - Parc de Salut Mar
Barcelona, 08003, Spain
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
Barcelona, 08908, Spain
Hospital San Pedro de Alcantara
Cáceres, 10003, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Universitario Marqués de Valdecilla
Santander, 39008, Spain
Hospital Universitario Virgen del Rocío
Seville, 41013, Spain
Hospital Arnau de Vilanova
Valencia, 25198, Spain
Istituto Oncologico della Svizzera Italiana
Bellinzona, 6500, Switzerland
Özel Koru Hastanesi
Çukurambar, Ankara, 6510, Turkey (Türkiye)
VKV Amerikan Hastanesi
Şişli, Istanbul, 34365, Turkey (Türkiye)
Ege Universitesi Tip Fakultesi Hastanesi
Bornova, İzmir, 35100, Turkey (Türkiye)
Ondokuz Mayis Üniversitesi
Kurupelit, Samsun, 55270, Turkey (Türkiye)
Karadeniz Teknik Üniversitesi Tip Fakültesi
Ortahisar, Trabzon, 61080, Turkey (Türkiye)
Ankara Universitesi Tip Fakultesi - Cebeci Arastirma ve Uygulama Hastanesi
Ankara, 06100, Turkey (Türkiye)
Mehmet Kemal Dedeman Hematoloji Hastanesi
Kayseri, 38039, Turkey (Türkiye)
The Royal Marsden NHS Foundation Trust
Sutton, England, SM2 5PT, United Kingdom
NHS Greater Glasgow and Clyde
Glasgow, G12 0XH, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 8, 2020
First Posted
May 12, 2020
Study Start
September 16, 2020
Primary Completion
March 31, 2026
Study Completion (Estimated)
June 30, 2028
Last Updated
April 28, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share