Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Refractory Diffuse Large B-Cell Lymphoma Clinical Trial

— LOTIS 5  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04384484
• Other study ID #: ADCT-402-311
• Secondary ID: 2020-000241-14
• Status: Recruiting
• Phase: Phase 3
• Start date: September 16, 2020
• Est. completion date: June 30, 2028

Study information

• Verified date: March 2024
• Source: ADC Therapeutics S.A.
• Contact: ADC Therapeutics
• Phone: 954-903-7994
• Email: clinical.trials[@]adctherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: June 30, 2028
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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
• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available) Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred [For China only: This inclusion criterion is not applicable]
• ECOG performance status 0-2
• Adequate organ function as defined by screening laboratory values within the following

parameters:

1. Absolute neutrophil count =1000/µL (off growth factors for at least 72 hours)

2. Platelet count =100000/µL without transfusion within the past 2 weeks

3. ALT, AST, and GGT =2.5 × the upper limit of normal (ULN)

4. Total bilirubin =1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to =3 × ULN)

5. 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 (ß-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.

Exclusion Criteria:

• 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
• Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary
• 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:

1. CD4+ T-cell (CD4+) counts <350 cells/µL

2. Acquired immunodeficiency syndrome-defining opportunistic infection within 12 months prior to screening

3. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of screening

4. 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
• Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis
• Lymphoma with active CNS involvement, including leptomeningeal disease
• Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
• Breastfeeding or pregnant
• Uncontrolled hypertension (blood pressure =160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, severe chronic pulmonary disease, or other serious medical condition which is likely to significantly impair the participant's ability to tolerate the study treatment
• Major surgery within 4 weeks prior to start of study drug (Cycle 1 Day 1); radiotherapy, chemotherapy or other antineoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1), except shorter if approved by the Sponsor
• Use of any other experimental medication within 14 days or 5 half-lives prior to start of study drug (Cycle 1 Day 1)
• Received live vaccine within 4 weeks of Cycle 1 Day 1
• Failure to recover to =Grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (except alopecia) due to previous therapy prior to screening
• Congenital long QT syndrome or a corrected QTcF interval of =480 ms at screening (unless secondary to pacemaker or bundle branch block)
• Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk
• Known history of hypersensitivity to oxaliplatin or other platinum-based drugs, or gemcitabine, or rituximab, or any of their excipients

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Refractory Diffuse Large B-Cell Lymphoma
• Relapsed Diffuse Large B-Cell Lymphoma

Intervention

Drug:
• Loncastuximab Tesirine
Intravenous Infusion
• Rituximab
Intravenous Infusion
• Gemcitabine
Intravenous Infusion
• Oxaliplatin
Intravenous Infusion

Locations

Country	Name	City	State
Argentina	Clinica Adventista Belgrano	Belgrano	Buenos Aires
Argentina	Instituto Médico Especializado Alexander Fleming	Buenos Aires	Distrito Federal
Argentina	Grupo Gamma - Hospital Privado Rosario	Rosario	Santa Fe
Argentina	Clínica de Nefrología, Urología y Enfermedades Cardiovasculares S.A.	Santa Fe	Buenos Aires
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Centre Hospitalier Universitaire Universite Catholique de Louvain	Namur
Belgium	Algemeen Ziekenhuis Delta - Campus Rumbeke	Roeselare
Brazil	Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer	Curitiba	Paraná
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Mãe de Deus - Centro Integrado de Oncologia	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Moinhos de Vento	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital do Câncer	Rio De Janeiro
Brazil	A Beneficência Portuguesa de São Paulo - Unidade Mirante	São Paulo
Brazil	Hemomed Instituto de Oncologia e Hematologia	São Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Brazil	Hospital Israelita Albert Einstein	São Paulo
Brazil	Hospital Santa Marcelina	São Paulo
Canada	Cross Cancer Institute	Edmonton
Canada	Research Institute of the McGill University Health Centre	Montréal
Canada	Hôpital Fleurimont	Sherbrooke
Chile	CeCim - Centro de Estudios Clínicos e Investigaciones Médicas	Santiago	Región Metropolitana De Santiago
Chile	Centro de Estudios Clínicos SAGA	Santiago	Región Metropolitana De Santiago
Chile	Instituto Oncológico Fundación Arturo López Pérez	Santiago	Región Metropolitana De Santiago
China	Peking University Third Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	West China School of Medicine - West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing University Cancer Hospital - Chongqing Cancer Hospital	Chongqing
China	Second Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Huizhou Municipal Central Hospital	Huizhou
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Shanghai Cancer Center	Shanghai	Shanghai
China	Institute of Hematology and Blood Diseases Hospital of CAMS - PUMC	Tianjin
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Tongji Hospital	Wuhan
China	Wuhan Union Hospital	Wuhan
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Henan Cancer Hospital - Zhengzhou University	Zhengzhou	Henan
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Fakultni Nemocnice Kralovske Vinohrady	Prague
Czechia	Fakultni nemocnice v Motole	Prague
France	Hôpital Avicenne	Bobigny
France	Centre Hospitalier Regional Universitaire Brest	Brest
France	Centre Hospitalier Regional Universitaire Brest	Brest	Bretagne
France	Hôpital Privé du Confluent	Nantes
France	Hopital Universitaire Pitie Salpetriere	Paris
France	Hôpital Haut-Lévêque	Pessac
France	Centre de Lutte Contre le Cancer - Centre Henri-Becquerel	Rouen
Hungary	Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet - Szent László	Budapest	Pest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet	Heves	Budapest
Israel	Samson Assuta Ashdod University Hospital	Ashdod
Israel	Soroka Medical Center	Be'er Sheva
Israel	Shamir Medical Center (Assaf Harofeh)	Be'er Ya'aqov
Israel	Carmel Medical Center	Haifa
Israel	Rabin Medical Center - Beilinson Hospital	Petah tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel Aviv
Italy	Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliero - Universitaria Careggi	Florence
Italy	Ospedale Casa Sollievo della Sofferenza	Foggia
Italy	Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST	Meldola
Italy	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas	Milan
Italy	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele	Milan
Italy	Istituto Europeo di Oncologia	Milano
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Sanitaria Locale della Romagna	Ravenna
Italy	Presidio Ospedaliero Universitario Santa Maria della Misericordia	Udine	Friuli Venezia Giulia
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Bunkyo-ku	Tokyo
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Gifu Municipal Hospital	Gifu
Japan	Saitama Medical University - International Medical Center	Hidaka-Shi	Saitama
Japan	Kagoshima University Hospital	Kagoshima
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Matsuyama Red Cross Hospital	Matsuyama	Ehime
Japan	Nagasaki University Hospital	Nagasaki-city	Nagasaki
Japan	National Hospital Organization - Nagoya Medical Center	Nagoya	Aichi
Japan	Niigata University Medical and Dental Hospital	Niigata
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Osaka Prefectural Hospital Organization - Osaka International Cancer Institute	Osaka
Japan	Gunma Prefectural Cancer Center	Ota	Gunma
Japan	Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Sapporo Hokuyu Hospital	Sapporo	Hokkaido
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	National Hospital Organization Disaster Medical Center	Tachikawa	Tokyo
Japan	Toyohashi Municipal Hospital	Toyohashi	Aichi
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Mexico	PanAmerican Clinical Research Mexico - Cuernavaca	Cuernavaca	Morelos
Mexico	Boca Raton Clinical Research (BRCR) Global Mexico - Guadalajara	Guadalajara	Jalisco
Mexico	PanAmerican Clinical Research Mexico - Guadalajara	Guadalajara	Jalisco
Mexico	Hematológica Alta Especialidad	Huixquilucan
Mexico	Boca Raton Clinical Research (BRCR) Global Mexico - Ciudad de México	Mexico City
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey	Nuevo Leon
Netherlands	Hagaziekenhuis Van Den Haag - Leyweg	Den Haag	South Holland
Netherlands	Elisabeth-TweeSteden Ziekenhuis - Elisabeth	Tilburg
Poland	Szpitale Pomorskie Spólka Z Ograniczona Odpowiedzialnoscia	Gdynia
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia MCM Kraków	Kraków	Malopolskie
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lódz
Poland	Szpital Wojewódzki w Opolu	Opole
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Poland	Instytut Hematologii I Transfuzjologii	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Puerto Rico	Hospital Español Auxilio Mutuo	San Juan
Spain	Hospital del Mar - Parc de Salut Mar	Barcelona
Spain	Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Arnau de Vilanova	Valencia
Switzerland	Istituto Oncologico della Svizzera Italiana	Bellinzona
Turkey	Ankara Universitesi Tip Fakultesi - Cebeci Arastirma ve Uygulama Hastanesi	Ankara
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Bornova	Izmir
Turkey	Özel Koru Hastanesi	Çukurambar	Ankara
Turkey	Mehmet Kemal Dedeman Hematoloji Hastanesi	Kayseri
Turkey	Ondokuz Mayis Üniversitesi	Kurupelit	Samsun
Turkey	Karadeniz Teknik Üniversitesi Tip Fakültesi	Ortahisar	Trabzon
Turkey	VKV Amerikan Hastanesi	Sisli	Istanbul
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	England
United States	Hollings Cancer Center	Charleston	South Carolina
United States	UnityPoint Health - Iowa Oncology Research Association (IORA)	Des Moines	Iowa
United States	Virginia Cancer Specialists	Gainesville	Virginia
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada - Henderson	Las Vegas	Nevada
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Medical College of Wisconsin Cancer Center Clinical Trials Office	Milwaukee	Wisconsin
United States	Kaiser Permanente Interstate Medical Office Central	Portland	Oregon
United States	Redlands Community Hospital	Redlands	California
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
ADC Therapeutics S.A.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  France,  Hungary,  Israel,  Italy,  Japan,  Mexico,  Netherlands,  Poland,  Puerto Rico,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)		Up to 4 years
Secondary	Overall Survival (OS)		Up to 4 years
Secondary	Overall Response Rate (ORR)		Up to 4 years
Secondary	Complete Response Rate (CRR)		Up to 4 years
Secondary	Duration of Response (DOR)		Up to 4 years
Secondary	Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE)		Day 1 up to a maximum of Week 39
Secondary	Number of Participants Who Experience At Least One Serious Adverse Event (SAE)		Up to 4 years
Secondary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results		Day 1 up to a maximum of Week 25
Secondary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements		Day 1 up to a maximum of Week 25
Secondary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Physical Examinations		Day 1 up to a maximum of Week 25
Secondary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status		Day 1 up to a maximum of Week 25
Secondary	Number of Participants Who Experience a Clinically Significant Change From Baseline in Electrocardiogram (ECG) Results		Day 1 up to a maximum of Week 25
Secondary	Average Concentration of Loncastuximab Tesirine at the End of Infusion		Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)
Secondary	Average Concentration of Loncastuximab Tesirine Before Infusion		Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)
Secondary	Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine		Day 1 up to a maximum of Week 25
Secondary	Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Core 30 (EORTC QLQ-C30)		Baseline up to a maximum of Week 25
Secondary	Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Lymphoma Subscale of Functional Assessment of Cancer Therapy- Lymphoma (LymS of FACT-Lym)		Baseline up to a maximum of Week 25
Secondary	Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by GP5 Item of the Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)		Baseline up to a maximum of Week 25
Secondary	Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)		Baseline to up to 4 years