A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Adult Patients With B-cell Non-Hodgkin Lymphoma Who Have Been Previously Treated With Other Cancer Therapies
- Registration Number
- NCT03888105
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching an investigational drug, odronextamab, in adult patients B-cell non-Hodgkin's lymphoma (B-NHL).
The main purpose of this study is to assess the effectiveness of odronextamab in destroying cancer cells and to learn more about the safety of odronextamab.
The study is looking at several other research questions, including:
* To see if odronextamab works to destroy cancer cells
* Side effects that may be experienced by people taking odronextamab
* How odronextamab works in the body
* How much odronextamab is present in the blood
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 576
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For the FL grade 1-3a cohort only: Central histopathologic confirmation of the FL Grade 1 to 3a diagnosis must be obtained before study enrollment. Patients with FL grade 3b are ineligible for this cohort but may be included in the "other B-NHL" cohort. Follicular lymphoma subtyping is based on the World Health Organization (WHO) classification (Swerdlow, 2017).
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Disease-specific cohorts:
Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment.
- FL grade 1-3a cohort: Patients with FL grade 1-3a that has relapsed after or is refractory to at least 2 prior lines of systemic therapy, as defined in the protocol
- DLBCL cohort: Patients with DLBCL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol
- MCL after BTK inhibitor therapy cohort: Patients with MCL who have relapsed or refractory disease to at least one prior line of systemic therapy and had prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor.
- MZL cohort: Patients with MZL that have relapsed or is refractory to at least 2 prior lines of systemic therapy.
- Other B-NHL cohort: Patients with B-NHL other than FL grade 1-3a, DLBCL, MCL, or MZL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol. New enrollment stopped for patients with Burkitt lymphoma and Burkitt-like lymphoma.
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Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI)
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Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
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Adequate bone marrow, hepatic, and renal function as defined in the protocol
Key
- Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS Non-Hodgkin Lymphoma (NHL) (suspected CNS lymphoma should be evaluated by lumbar puncture, as appropriate, in addition to the mandatory head CT or MRI).
- Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 28 days prior to first administration of study drug, whichever is shorter.
- History of allogeneic stem cell transplantation
- Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug
- History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded
- Another malignancy except B-NHL in the past 5 years, with the exception of non-melanoma skin cancer that has undergone potentially curative therapy or in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent.
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; cytomegalovirus (CMV) infection as noted by detectable levels on a blood polymerase chain reaction (PCR) assay as defined in the protocol or other uncontrolled infections
- Known hypersensitivity to both allopurinol and rasburicase
- Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy
Note: Other protocol-defined Inclusion/Exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FL Odronextamab Follicular lymphoma grade 1-3a cohort DLBCL Odronextamab Diffuse large B-cell lymphoma cohort MZL Odronextamab Marginal Zone Lymphoma cohort MCL Odronextamab Mantle Cell Lymphoma cohort Other B-NHL Odronextamab Other B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia \[WM\]); Patients with a current diagnosis of mixed histology of B-NHL with an aggressive component (such as concurrent FL and DLBCL) will be allowed
- Primary Outcome Measures
Name Time Method Objective response rate (ORR), as assessed by independent central review Up to 52 weeks of study treatment FL grade 1-3a/MZL
ORR, as assessed by independent central review Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
- Secondary Outcome Measures
Name Time Method ORR, as assessed by the local investigator Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
Complete response (CR) rate, as assessed by the local investigator Up to 52 weeks of study treatment FL grade 1-3a/MZL
CR rate, as assessed by independent central review Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
CR rate, as assessed by the local investigator Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
Progression-free survival (PFS), as assessed by independent central review Approximately 194 weeks following the first dose PFS, as assessed by the local investigator Approximately 194 weeks following the first dose Overall survival (OS) Approximately 194 weeks following the first dose Duration of response (DOR), as assessed by independent central review Approximately 194 weeks following the first dose DOR, as assessed by the local investigator Approximately 194 weeks following the first dose DCR, as assessed by independent central review Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
DCR, as assessed by the local investigator Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
Incidence of anti-drug antibodies (ADA) to odronextamab over time 12 weeks following end of treatment Incidence of neutralizing antibodies (Nab) to odronextamab over time 12 weeks following end of treatment Changes in scores of patient-reported outcomes as measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30) Approximately 194 weeks following the first dose The EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties).
Disease control rate (DCR), as assessed by independent central review Up to 52 weeks of study treatment FL grade 1-3a/MZL
DCR, as assessed by the local ivestigator Up to 52 weeks of study treatment FL grade 1-3a/MZL
Incidence and severity of treatment emergent adverse events (TEAEs) Approximately 194 weeks following the first dose Concentration of odronextamab 12 weeks following end of treatment End of infusion \[EOI\]; Concentration at a specified time t \[Ct\])
Titer of anti-drug antibodies to odronextamab over time 12 weeks following end of treatment Changes in scores of patient-reported outcomes as measured by Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) Approximately 194 weeks following the first dose Composed of the FACT-G plus the 15-item Lymphoma Subscale (LymS).
Changes in scores of patient-reported outcomes as measured by EuroQol-5 Dimensions-3 Levels (EQ-5D-3L) Approximately 194 weeks following the first dose The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.
Trial Locations
- Locations (140)
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Azienda Ospedaliera Santa Maria Terni
🇮🇹Terni, Italy
Ospedale dell'Angelo - Varese
🇮🇹Varese, Italy
Ospedale DellAngelo Di Mestre
🇮🇹Venice, Italy
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Chang Gung Memorial Hospital Kaohsiung
🇨🇳Kaohsiung City, Taiwan
North Building
🇦🇺Frankston, Victoria, Australia
Andrew Love Cancer Center
🇦🇺Tweed Heads, Australia
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
The First Bethune Hospital
🇨🇳Changchun, Jilin, China
Taipei Medical University - Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan
China Medical University
🇨🇳Taichung City, Taiwan
National Cheng Kung University
🇨🇳Tainan City, Taiwan
Chi-Mei Medical Center - Liuying
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Mackay Memorial Hospital
🇨🇳Taipei City, Taiwan
Szpitale Pomorskie spSp. Z.o.o.
🇵🇱Gdynia, Poland
Hospital de la Pitie-Salpetriere
🇫🇷Paris, France
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center at Hackensack UMC
🇺🇸Hackensack, New Jersey, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Weill Cornell Medical College New York Presbyterian Hospital
🇺🇸New York, New York, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Harold C. Simmons Comprehensive Cancer Center
🇺🇸Dallas, Texas, United States
San Antonio Military Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Border Medical Oncology
🇦🇺East Albury, New South Wales, Australia
Northern NSW Local Health District The Tweed Hospital
🇦🇺Tweed Heads, South Wales, Australia
Epworth Hospital
🇦🇺East Melbourne, Victoria, Australia
Olivia Newton John Cancer Wellness & Research Centre
🇦🇺Heidelberg, Victoria, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
QEII Health Science Centre - Halifax location
🇨🇦Halifax, Nova Scotia, Canada
Peking University Cancer Hospital (Beijing Cancer Hospital) (Beijing Institute for Cancer Research)
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Institute of Hematology & Blood Diseases Hospital
🇨🇳Tianjin, Beijing, China
Second Affiliated Hospital - Xinqiao Hospital
🇨🇳Chongqing, Chongqing, China
Sun Yat-Sen University Cancer Center - Cancer Prevention and Treatment Center, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
The Affiliated Tumor Hospital
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Renmin Hospital of Wuhan University - Hubei Provincial People's Hospital
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital - Soochow University
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital of Xi 'an Jiaotong University
🇨🇳Xi'an, Shaanxi, China
Shanhai Cancer Center
🇨🇳Shanghai, Shanghai, China
West China Hospital
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University Cancer Institute
🇨🇳Tianjin, Tianjin, China
The First Hospital affiliated to the Medical School of Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Peking University - Third Hospital
🇨🇳Beijing, China
Hopital Haut-Leveque
🇫🇷Pessac, Aquitaine, France
Centre Hospitalier Universitaire de Caen - Hematologie Clinique IHBN
🇫🇷Caen, Calvados, France
Unite Hemopathies Lymphoides Hospital Henri Mondor
🇫🇷Créteil, Ile-de-France, France
CHU Hotel Dieu Service Hematologie
🇫🇷Nantes, Loire, France
Hopital Lyon Sud
🇫🇷Pierre-Benite, Lyon, France
Hopital Claude Huriez - CHR Lille
🇫🇷Lille, Nord, France
Chu Poitiers - Pole Regional De Cancerologie
🇫🇷Poitiers, Vienne, France
Hopital Saint Louis
🇫🇷Paris, France
Klinik fur Innere Medizin II - Schwarzwald Baar Klinikum
🇩🇪Villingen-Schwenningen, Donaueschingen, Germany
Kliniken Ostalb Stauferklinikum Schwab Gmund
🇩🇪Mutlangen, Gmund, Germany
Klinikum Chemnitz
🇩🇪Chemnitz, Germany
University Hospital Halle Saale
🇩🇪Halle Saale, Germany
Universitatsklinik Wurzburg, Med Klinik und Poliklinik II, Zentrum Innere Medizin
🇩🇪Wurzburg, Germany
IRCCS Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
UOC Hematologia, Fondazione IRCCS, Ca Granda, OM Policlinico
🇮🇹Milano, Milan, Italy
University of Bologna Dipartimento di Medicina Specialistica Diagnostica e Sperimentale
🇮🇹Bologna, Italy
Azienda Ospedaliera Careggi
🇮🇹Firenze, Italy
Uos Ematologia - Ospedale Civile di Livorno
🇮🇹Livorno, Italy
ASST Grande Ospedale Metropolitano Niguarda - Division of Hematology
🇮🇹Milano, Italy
AOU Maggiore della Carita
🇮🇹Novara, Italy
Presidio Ospedaliero Santa Maria della Misericordia
🇮🇹Perugia, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
🇯🇵Nagoya, Aichi, Japan
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya, Aiti, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba-ken, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
National Hospital Organization National Kyushu Cancer Center
🇯🇵Fukuoka-shi, Hukuoka, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Hyogo, Japan
Tokai University Hospital
🇯🇵Isehara-Shi, Kanagawa, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto City, Kyoto, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka City, Osaka, Japan
Saitama Medical University International Medical Center
🇯🇵Hidaka, Saitama, Japan
Chiba Cancer Center
🇯🇵Chiba-shi, Tiba, Japan
National Cancer Center Hospital - Tsukiji Campus
🇯🇵Chuo ku, Tokyo, Japan
Yamagata University Hospital
🇯🇵Yamagata City, Yamagata Prefecture, Japan
Japanese Red Cross Nagasaki Genbaku Hospital
🇯🇵Nagasaki, Japan
Keimyung University Dongsan Medical Center
🇰🇷Daegu si, Daegu, Korea, Republic of
University of Ulsan College of Medicine
🇰🇷Ulsan, Daegu, Korea, Republic of
National Cancer Center
🇰🇷Gyeonggi do, Gyeonggi, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Gyeonggi, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital - Hemato Oncology
🇰🇷Seoul, Korea, Republic of
Matopolskie Centrum Medyczne S.C.
🇵🇱Krakow, Malopolskie, Poland
Centrum Onkologii Instytut im M Sklodowskiej CurieOddzial Chorob United Kingdomladu Chlonnego
🇵🇱Warszawa, Mazowieckie, Poland
Uniwersyteckie Centrum
🇵🇱Gdansk, Pomorskie, Poland
Pomorskie Hospitals SP. Z O. O. Oncology And Radiotherapy Ward
🇵🇱Gdynia, Pomorskie, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika w Lodzi (Copernicus Memorial Hospital)
🇵🇱Lodz, Poland
Instytut Hematologii I Transfuzjologii Klinika Hematologii
🇵🇱Warszawa, Poland
Uniwersytecki Szpital Kliniczny we Wroclawiu, Klinika Hematologii, Terapii Komorkowych i Chorob Wewnetrznych
🇵🇱Wroclaw, Poland
National University Hospital
🇸🇬Singapore, Singapore
Singapore General Hospital
🇸🇬Singapore, Singapore
Raffles Cancer Centre
🇸🇬Singapore, Singapore
Icon Soc Farrer Park
🇸🇬Singapore, Singapore
Hospital Universitari Son Espases
🇪🇸Palma, Balearic Islands, Spain
Ico Lhospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Catalonia, Spain
Hospital Universitario Donostia
🇪🇸Donostia, Gipuzkoa, Spain
Hospital Son Llatzer
🇪🇸Palma, Illes Balears, Spain
Hospital Universitario Quiron Salud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Costa del Sol
🇪🇸Marbella, Malaga, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona - Planta 4 Escalera
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
MD Anderson Cancer Center- Madrid
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei City, Taiwan
Tri-Service General Hospital
🇨🇳Taipei City, Taiwan
Chang Gung Medical Foundation-
🇨🇳Taoyuan, Taiwan
Royal Cornwall Hospital
🇬🇧Truro, Cornwall, United Kingdom
Derriford Hospital and the Royal Eye Infirmary
🇬🇧Plymouth, Devon, United Kingdom
Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom