A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Patients With Previously Untreated Diffuse Large B-cell Lymphoma
- Conditions
- Diffuse Large B-cell Lymphoma (DLBCL)
- Interventions
- Drug: Prednisone/Prednisolone
- Registration Number
- NCT06091865
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching an experimental drug called odronextamab, referred to as study drug, when used in combination with chemotherapy. The study is focused on patients with diffuse large B-cell lymphoma (DLBCL) that have not been treated before (called "previously untreated"). Patients with DLBCL that have come back after treatment (called "relapsed"), or have not responded to treatment (called "refractory"), can also participate in this study.
This study will be made up of Part 1A, Part 1B, and Part 2.The aim of Part 1A and Part 1B of the study is to see how safe and tolerable the study drug in combination with chemotherapy is and to determine the dose and schedule of the study drug to be combined with chemotherapy in Part 2 of the study.
The aim of Part 2 of the study is to see how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab (the comparator drug), and chemotherapy, the current standard of care treatment approved for DLBCL. Standard of care means the usual medication expected and used when receiving treatment for a condition.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug when combined with chemotherapy
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)
* The impact from the study drug on quality of life and ability to complete routine daily activities
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 904
- Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL, for whom next available standard of care therapy is not available or deemed ineligible according to the investigator (Part 1A only)
- Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Life expectancy ≥ 12 months
- International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only;
- Adequate hematologic and organ function, as defined in the protocol.
KEY
- Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology
- Another active malignancy, significant active disease or medical condition, as described in the protocol
- Peripheral neuropathy Grade ≥3
- Treatment with any systemic anti-lymphoma therapy, except for participants with relapsed/refractory (R/R) DLBCL and participants with DLBCL transformed from an indolent follicular lymphoma after treatment with systemic anti-lymphoma therapy.
- Any other therapy or investigational treatment within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment
- Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol
- Allergy/hypersensitivity to study drugs, as described in the protocol
- Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus disease (COVID-19) infection, uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol.
Note: Other protocol-defined Inclusion/ Exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Odronextamab + CHOP Doxorubicin Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B). Odronextamab + CHOP Vincristine Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B). Odronextamab + CHOP Prednisone/Prednisolone Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B). Rituximab + CHOP Prednisone/Prednisolone Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP. Odronextamab + CHOP Cyclophosphamide Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B). Rituximab + CHOP Rituximab Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP. Rituximab + CHOP Cyclophosphamide Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP. Rituximab + CHOP Doxorubicin Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP. Rituximab + CHOP Vincristine Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP. Odronextamab + CHOP Odronextamab Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).
- Primary Outcome Measures
Name Time Method Incidence of dose limiting toxicities (DLTs) Up to 35 days Part 1A
Incidence of treatment emergent adverse events (TEAEs) Up to 2 years Part 1
Severity of TEAEs Up to 2 years Part 1
Progression free survival (PFS), assessed by independent central review (ICR) Up to 5 years Part 2
- Secondary Outcome Measures
Name Time Method Complete response (CR) assessed by ICR Up to 22 weeks Part 2
Overall survival (OS) Up to 5 years Part 2
Best Overall response (BOR) as assessed by local investigators Up to 22 weeks Part 1 and Part 2
CR as assessed by local investigators Up to 22 weeks Part 1 and Part 2
Duration of response (DOR) as assessed by local investigators Up to 5 years Part 1 and Part 2
Odronextamab concentrations in serum when administered with CHOP Up to 22 weeks Part 1 and Part 2
Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration Up to 22 weeks Part 1 and Part 2
Titer of ADA to odronextamab over the study duration Up to 22 weeks Part 1 and Part 2
Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration Up to 22 weeks Part 1 and Part 2
PFS assessed by local investigator review Up to 5 years Part 2
EFS assessed by local investigator review Up to 5 years Part 2
BOR assessed by ICR Up to 22 weeks Part 2
DOR assessed by ICR Up to 5 years Part 2
Incidence of TEAEs Up to 2 years Part 2
Severity of TEAEs Up to 2 years Part 2
Measurable Residual Disease (MRD) status Up to 22 weeks Part 2
Duration of MRD-negativity Up to 5 years Part 2
Event-free survival (EFS) assessed by ICR Up to 5 years Part 2
Change in physical functioning as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30 Up to 5 years Part 2 The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.
Change in patient reported outcomes, as measured by EORTC QLQ-C30 Up to 5 years Part 2 The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.
Change in patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) Up to 5 years Part 2 The FACT-Lym lymphoma subscale (LymS) includes 15 items to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). Higher scores are associated with a worse quality of life.
Change in patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS) Up to 5 years Part 2 The PGIS includes a single-item to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. Patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 5-point scale ranging from 1 (No symptoms) to 4 (Very Severe).
Change in patient reported outcomes, as measured by Patient Global Impression of Change (PGIC) Up to 5 years Part 2 The PGIC item includes a single-item to assess how a patient perceives their overall change in health status since the start of study treatment. Patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse.
Change in patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L) Up to 5 years Part 2 The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".
Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item Up to 5 years Part 2 A single item (GP5) of the validated FACT-G questionnaire will be used to assess from the participant perspective the overall impact of treatment side-effect. The question item is on a 5-point scale ranging from "not at all" (0) to "very much" (4).
Trial Locations
- Locations (149)
Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Ampang
🇲🇾Ampang, Pahang, Malaysia
Hospital General Universitario de Toledo
🇪🇸Toledo, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
University Hospital Doctor Peset
🇪🇸Valencia, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Yeouido St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Centrum Innowacyjnych Terapii Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
🇵🇱Lublin, Poland
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
University of California (UC) Davis
🇺🇸Sacramento, California, United States
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
🇺🇸Indianapolis, Indiana, United States
St Vincent Ascension at Peyton Manning Childrens Hospital
🇺🇸Indianapolis, Indiana, United States
Investigative Clinical Research of Indiana
🇺🇸Noblesville, Indiana, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Clinical Research Alliance Inc
🇺🇸Westbury, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Center for Oncology and Blood Disorders
🇺🇸Houston, Texas, United States
Community Cancer Trials of Utah
🇺🇸Ogden, Utah, United States
Prohealth Care Inc
🇺🇸Waukesha, Wisconsin, United States
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Icon Cancer Centre - Wesley
🇦🇺Auchenflower, Queensland, Australia
Pindara Private Hospital
🇦🇺Benowa, Queensland, Australia
Epworth Freemasons
🇦🇺East Melbourne, Victoria, Australia
Landeskrankenhaus Hochsteiermark
🇦🇹Leoben, Styria, Austria
Kepler University Hospital
🇦🇹Linz, Upper Austria, Austria
Medical University Graz
🇦🇹Graz, Austria
Medical University of Vienna
🇦🇹Vienna, Austria
Hanusch Krankenhaus
🇦🇹Vienna, Austria
Klinikum Wels-Grieskirchen
🇦🇹Wels, Austria
AZ St.-Elisabeth Herentals vzw
🇧🇪Herentals, Antwerp, Belgium
Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital
🇧🇪Gent, Oost-Vlaanderen, Belgium
Az Delta
🇧🇪Roeselare, West Vlaanderen, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Centre Hospitalier Regional de Verviers
🇧🇪Verviers, Belgium
Hospital Clinico Universidad de Los Andes
🇨🇱Santiago, Las Condes, Chile
Inmunocel
🇨🇱Santiago, Region Metropolitana, Chile
Clinica Alemana de Santiago
🇨🇱Santiago, Chile
University Hospital Hradec Kralove
🇨🇿Hradec Kralove, East Bohemia, Czechia
University Hospital Kralovske Vinohrady
🇨🇿Prague, Czechia
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Praha, Czechia
Centre Hospitalier Universitaire (CHU) Rennes
🇫🇷Rennes, Bretagne, France
CHRU de Tours
🇫🇷Tours, Centre Val De Loire, France
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux Cedex, Gironde, France
Hopital Victor Dupouy Argenteuil
🇫🇷Argenteuil, Ile De France, France
Avicenne Hospital
🇫🇷Bobigny, Ile De France, France
Hopital Saint Vincent-de-Paul
🇫🇷Lille, Nord, France
CHU de Poitiers
🇫🇷Poitiers, Nouvelle Aquitaine, France
Centre Hospitalier Universitaire (CHU) de Bordeaux
🇫🇷Pessac, Nouvelle-Aquitaine, France
Nantes University Hospital
🇫🇷Nantes, Pays De La Loire, France
Centre Hospitalier Metropole Savoie
🇫🇷Chambery, Savoie, France
Gustave Roussy
🇫🇷Villejuif, Val De Marne / Ile De France, France
Centre Hospitalier Universitaire Angers
🇫🇷Angers, France
Change Annecy
🇫🇷Metz Tessy, France
CHU Nimes Institut de Cancerologie
🇫🇷Nimes, France
Assistance Publique-Hopitaux de Paris (AP-HP)
🇫🇷Paris, France
CHU de Saint-Etienne
🇫🇷Saint-Etienne, France
Robert-Bosch-Krankenhaus
🇩🇪Stuttgart, Baden-Wurttemberg, Germany
Kliniken Ostalb Stauferklinikum Schwab Gmund
🇩🇪Mutlangen, Gmund, Germany
Clinic Frankfurt (Oder)
🇩🇪Frankfurt, Hesse, Germany
University Hospital Essen
🇩🇪Essen, Nordrhein Westfalen, Germany
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
🇩🇪Mainz, Rheinland-Pfalz, Germany
Hematological Praxis Dresden
🇩🇪Dresden, Sachsen, Germany
University Hospital Carl Gustav Carus
🇩🇪Dresden, Germany
Stadtisches Krankenhaus Kiel
🇩🇪Kiel, Germany
Beaumont Hospital
🇮🇪Dublin, Leinster, Ireland
St James Hospital and Trinity College Dublin
🇮🇪Dublin, Ireland
The Chaim Sheba Medical Center
🇮🇱Tel-Hashomer, Tel Aviv, Israel
Samson Assuta Ashdod University Hospital
🇮🇱Ashdod, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
The Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola (fc), Forli Cesena, Italy
ASST Monza Ospedale San Gerardo
🇮🇹Monza, Lombardy, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
A.O.U. di Modena
🇮🇹Modena, Italy
Federico II University
🇮🇹Napoli, Italy
AOU Maggiore della Carita
🇮🇹Novara, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Azienda Ospedaliera di Perugia
🇮🇹Perugia, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
Hematology - Città della Salute e della Scienza di Torino
🇮🇹Turin, Italy
Santa Maria della Misericordia
🇮🇹Udine, Italy
St. Vincent Hospital - The Catholic University of Korea
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Namdong-Gu, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Yeyungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Tg Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Sabah, Malaysia
Subang Jaya Medical Center
🇲🇾Subang Jaya, Selangor, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia
Uniwersytecki Szpital Kliniczny
🇵🇱Wroclaw, Dolnoslaskie, Poland
Matopolskie Centrum Medyczne S.C.
🇵🇱Krakow, Malopolskie, Poland
Pratia Poznan Medical Center
🇵🇱Poznan, Wielkopolska, Poland
Szpital Uniwersytecki Nr2 Bydgoszcz
🇵🇱Bydgoszcz, Poland
Uniwersyteckie Centrum Kliniczne, Building of the Non-Invasive Medicine Center
🇵🇱Gdansk, Poland
Szpital Szpecjalistyczny w Walbrzychu
🇵🇱Walbrzych, Poland
National University Hospital Singapore
🇸🇬Singapore, Singapore
National Cancer Centre of Singapore
🇸🇬Singapore, Singapore
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Hospital Clinico Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruna, Spain
Hospital Universitario Central De Asturias
🇪🇸Oviedo, Asturias, Spain
Son Espases University Hospital
🇪🇸Palma, Balearic Islands, Spain
Hospital Universitari Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Hospital Universitari Mutua Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Universitario de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Sant Pau
🇪🇸Barcelona, Spain
Hospital Virgen De Las Nieves De Granada
🇪🇸Granada, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Fundacion Jimenez Diaz University Hospital
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro, Servicio de Hematologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Changhua Christian Hospital
🇨🇳Changhua City, Taiwan
Taipei Medical University - Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan
Chang Gung Medical Foundation Chia Yi Branch
🇨🇳Puzi City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Wanfang Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital- Linkou Branch
🇨🇳Taoyuan, Taiwan
Chulalongkorn University
🇹🇭Bangkok, Krung Thep Maha Nakhon [Bangko], Thailand
Sriraj Hospital
🇹🇭Bangkok, Thailand
Chaing Mai University
🇹🇭Chiang Mai, Thailand
Faculty of Medicine
🇹🇭Khon Kaen, Thailand
Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
🇹🇷Yenimahalle, Ankara, Turkey
VM Medical Park Mersin Hospital
🇹🇷Mezitli, Mersin, Turkey
Tekirdag Namik Kemal University Hospital
🇹🇷Tekirdag, Suleymanpasa, Turkey
Gazi Universitesi
🇹🇷Besevler, Turkey
Istanbul University Istanbul Faculty of Medicine
🇹🇷Istanbul, Turkey
Ege University
🇹🇷Izmir, Turkey
Dokuz Eylul University
🇹🇷Izmir, Turkey
Sakarya Universty Medical Faculty
🇹🇷Sakarya, Turkey
Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
🇹🇷Samsun, Turkey
NHS Grampian: Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
The Hillingdon Hospitals NHS Foundation Trust
🇬🇧Uxbridge, United Kingdom