Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (LOTIS 5)
Relapsed Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
About this trial
This is an interventional treatment trial for Relapsed Diffuse Large B-Cell Lymphoma focused on measuring Loncastuximab Tesirine, Refractory Diffuse Large B-Cell Lymphoma, Relapsed Diffuse Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Lymphoma
Eligibility Criteria
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
- 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
- Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy
- 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
- 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 6 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 or 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:
- 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
- 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
Sites / Locations
- University of California San Diego Moores Cancer CenterRecruiting
- Redlands Community HospitalRecruiting
- The Oncology Institute of Hope and InnovationRecruiting
- Baptist MD Anderson Cancer CenterRecruiting
- UnityPoint Health - Iowa Oncology Research Association (IORA)Recruiting
- Norton Cancer InstituteRecruiting
- Comprehensive Cancer Centers of Nevada - HendersonRecruiting
- Kaiser Permanente Interstate Medical Office CentralRecruiting
- Hollings Cancer CenterRecruiting
- Texas Oncology Corporate Office
- Huntsman Cancer Institute and Hospital
- Virginia Cancer SpecialistsRecruiting
- Medical College of Wisconsin Cancer Center Clinical Trials OfficeRecruiting
- Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-JanRecruiting
- Cliniques Universitaires Saint-LucRecruiting
- Centre Hospitalier Universitaire Universite Catholique de LouvainRecruiting
- Algemeen Ziekenhuis Delta - Campus RumbekeRecruiting
- Cross Cancer InstituteRecruiting
- Research Institute of the McGill University Health CentreRecruiting
- Hôpital FleurimontRecruiting
- Peking University Third HospitalRecruiting
- The First Affiliated Hospital of Xiamen UniversityRecruiting
- Sun Yat-Sen University Cancer CenterRecruiting
- Guangdong Provincial People's HospitalRecruiting
- Zhujiang Hospital of Southern Medical UniversityRecruiting
- Henan Cancer Hospital - Zhengzhou UniversityRecruiting
- Jilin Cancer HospitalRecruiting
- The First Hospital of Jilin UniversityRecruiting
- Second Affiliated Hospital of Dalian Medical UniversityRecruiting
- Shanghai Cancer CenterRecruiting
- West China School of Medicine - West China Hospital of Sichuan UniversityRecruiting
- Tianjin Medical University Cancer Institute & HospitalRecruiting
- The First Affiliated Hospital of Zhejiang University School of MedicineRecruiting
- Chongqing University Cancer Hospital - Chongqing Cancer HospitalRecruiting
- Huizhou Municipal Central HospitalRecruiting
- The First Affiliated Hospital of Nanchang UniversityRecruiting
- Institute of Hematology and Blood Diseases Hospital of CAMS - PUMCRecruiting
- Wuhan Union HospitalRecruiting
- Tongji HospitalRecruiting
- Fakultni nemocnice OstravaRecruiting
- Fakultni Nemocnice Kralovske VinohradyRecruiting
- Fakultni nemocnice v MotoleRecruiting
- Hôpital AvicenneRecruiting
- Centre Hospitalier Regional Universitaire BrestRecruiting
- CHU Dijon Bourgogne - Hôpital François MitterrandRecruiting
- Hôpital Privé du ConfluentRecruiting
- Hopital Universitaire Pitie SalpetriereRecruiting
- Hôpital Haut-LévêqueRecruiting
- Centre de Lutte Contre le Cancer - Centre Henri-BecquerelRecruiting
- Semmelweis EgyetemRecruiting
- Orszagos Onkologiai IntezetRecruiting
- Samson Assuta Ashdod University HospitalRecruiting
- Soroka Medical CenterRecruiting
- Shamir Medical Center (Assaf Harofeh)Recruiting
- Carmel Medical CenterRecruiting
- Rabin Medical Center - Beilinson HospitalRecruiting
- The Chaim Sheba Medical CenterRecruiting
- Tel Aviv Sourasky Medical CenterRecruiting
- Presidio Ospedaliero Universitario Santa Maria della MisericordiaRecruiting
- Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di BresciaRecruiting
- Azienda Ospedaliero - Universitaria CareggiRecruiting
- Ospedale Casa Sollievo della SofferenzaRecruiting
- Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRSTRecruiting
- Istituto Europeo di OncologiaRecruiting
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico HumanitasRecruiting
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San RaffaeleRecruiting
- Fondazione IRCCS Policlinico San MatteoRecruiting
- Sanitaria Locale della RomagnaRecruiting
- Azienda Ospedaliera Universitaria Integrata VeronaRecruiting
- Boca Raton Clinical Research (BRCR) Global Mexico - GuadalajaraRecruiting
- PanAmerican Clinical Research Mexico - GuadalajaraRecruiting
- PanAmerican Clinical Research Mexico - CuernavacaRecruiting
- Hematológica Alta EspecialidadRecruiting
- Boca Raton Clinical Research (BRCR) Global Mexico - Ciudad de MéxicoRecruiting
- Hagaziekenhuis Van Den Haag - LeywegRecruiting
- Elisabeth-TweeSteden Ziekenhuis - ElisabethRecruiting
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we WrocławiuRecruiting
- Pratia MCM KrakówRecruiting
- Szpitale Pomorskie Spółka Z Ograniczoną OdpowiedzialnościąRecruiting
- Pratia Onkologia KatowiceRecruiting
- Szpital Wojewódzki w OpoluRecruiting
- Centrum Medyczne Pratia PoznańRecruiting
- Instytut Hematologii I TransfuzjologiiRecruiting
- Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w LodziRecruiting
- Hospital del Mar - Parc de Salut MarRecruiting
- Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)Recruiting
- Juan Miguel Bergua BurguesRecruiting
- Hospital Universitario Ramón y CajalRecruiting
- Hospital Universitario Fundación Jiménez DíazRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- Hospital Universitario La PazRecruiting
- Hospital Universitario Marqués de ValdecillaRecruiting
- Hospital Universitario Virgen del RocíoRecruiting
- Hospital Arnau de VilanovaRecruiting
- Istituto Oncologico della Svizzera ItalianaRecruiting
- The Royal Marsden NHS Foundation TrustRecruiting
- NHS Greater Glasgow and ClydeRecruiting
- The Christie NHS Foundation TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R)
Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R)
Part 2: Standard Immunochemotherapy (R-GemOx)
Part 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.
Randomized 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.
Randomized 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.