Clinical trial NCT03888105: 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
Official title: An Open-Label Study to Assess the Anti-Tumor Activity and Safety of REGN1979, an Anti CD20 x Anti-CD3 Bispecific Antibody, in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: B-cell Non-Hodgkin Lymphoma (B-NHL)
Keywords: Relapsed B-NHL
Refractory B-NHL
NHL
Follicular lymphoma (FL)
Diffuse large B-cell lymphoma (DLBCL)
Mantle cell lymphoma (MCL)
Marginal zone lymphoma (MZL)
bispecific antibody
CD20
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-03-25
Enrollment: 576
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 5 cohorts The first 68 patients in the DLBCL cohort will be randomized; the remaining patients will not be randomized
Primary purpose: TREATMENT

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


Eligibility criteria: Key Inclusion Criteria:

1. 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).
2. 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.
3. Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI)
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
5. Adequate bone marrow, hepatic, and renal function as defined in the protocol

Key Exclusion Criteria:

1. 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).
2. 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.
3. History of allogeneic stem cell transplantation
4. 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
5. History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded
6. 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.
7. 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
8. Known hypersensitivity to both allopurinol and rasburicase
9. Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Primary outcomes:
measure: Objective response rate (ORR), as assessed by independent central review
timeFrame: Up to 52 weeks of study treatment
measure: ORR, as assessed by independent central review
timeFrame: Up to 36 weeks of study treatment
Secondary outcomes:
measure: ORR, as assessed by the local investigator
timeFrame: Up to 52 weeks of study treatment
measure: ORR, as assessed by the local investigator
timeFrame: Up to 36 weeks of study treatment
measure: Complete response (CR) rate, as assessed by the local investigator
timeFrame: Up to 52 weeks of study treatment
measure: CR rate, as assessed by independent central review
timeFrame: Up to 52 weeks of study treatment
measure: CR rate, as assessed by the local investigator
timeFrame: Up to 36 weeks of study treatment
measure: CR rate, as assessed by independent central review
timeFrame: Up to 36 weeks of study treatment
measure: Progression-free survival (PFS), as assessed by independent central review
timeFrame: Approximately 194 weeks following the first dose
measure: PFS, as assessed by the local investigator
timeFrame: Approximately 194 weeks following the first dose
measure: Overall survival (OS)
timeFrame: Approximately 194 weeks following the first dose
measure: Duration of response (DOR), as assessed by independent central review
timeFrame: Approximately 194 weeks following the first dose
measure: DOR, as assessed by the local investigator
timeFrame: Approximately 194 weeks following the first dose
measure: Disease control rate (DCR), as assessed by independent central review
timeFrame: Up to 52 weeks of study treatment
measure: DCR, as assessed by the local ivestigator
timeFrame: Up to 52 weeks of study treatment
measure: DCR, as assessed by independent central review
timeFrame: Up to 36 weeks of study treatment
measure: DCR, as assessed by the local investigator
timeFrame: Up to 36 weeks of study treatment
measure: Incidence and severity of treatment emergent adverse events (TEAEs)
timeFrame: Approximately 194 weeks following the first dose
measure: Concentration of odronextamab
timeFrame: 12 weeks following end of treatment
measure: Incidence of anti-drug antibodies (ADA) to odronextamab over time
timeFrame: 12 weeks following end of treatment
measure: Titer of anti-drug antibodies to odronextamab over time
timeFrame: 12 weeks following end of treatment
measure: Incidence of neutralizing antibodies (Nab) to odronextamab over time
timeFrame: 12 weeks following end of treatment
measure: 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)
timeFrame: Approximately 194 weeks following the first dose
measure: Changes in scores of patient-reported outcomes as measured by Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym)
timeFrame: Approximately 194 weeks following the first dose
measure: Changes in scores of patient-reported outcomes as measured by EuroQol-5 Dimensions-3 Levels (EQ-5D-3L)
timeFrame: Approximately 194 weeks following the first dose
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Rogel Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack UMC
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College New York Presbyterian Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Dallas
country: United States
facility: Harold C. Simmons Comprehensive Cancer Center
state: Texas
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: East Albury
country: Australia
facility: Border Medical Oncology
state: New South Wales
city: Tweed Heads
country: Australia
facility: Northern NSW Local Health District The Tweed Hospital
state: South Wales
city: East Melbourne
country: Australia
facility: Epworth Hospital
state: Victoria
city: Frankston
country: Australia
facility: North Building
state: Victoria
city: Heidelberg
country: Australia
facility: Olivia Newton John Cancer Wellness & Research Centre
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Tweed Heads
country: Australia
facility: Andrew Love Cancer Center
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Science Centre - Halifax location
state: Nova Scotia
city: Beijing
country: China
facility: Peking University Cancer Hospital (Beijing Cancer Hospital) (Beijing Institute for Cancer Research)
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Beijing
city: Chongqing
country: China
facility: Second Affiliated Hospital - Xinqiao Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center - Cancer Prevention and Treatment Center, Sun Yat-sen University
state: Guangdong
city: Harbin
country: China
facility: The Affiliated Tumor Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University - Hubei Provincial People's Hospital
state: Hubei
city: Suzhou
country: China
facility: The First Affiliated Hospital - Soochow University
state: Jiangsu
city: Changchun
country: China
facility: The First Bethune Hospital
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Shanghai
country: China
facility: Shanhai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute
state: Tianjin
city: Hangzhou
country: China
facility: The First Hospital affiliated to the Medical School of Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Beijing
country: China
facility: Peking University - Third Hospital
city: Pessac
country: France
facility: Hopital Haut-Leveque
state: Aquitaine
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen - Hematologie Clinique IHBN
state: Calvados
city: Créteil
country: France
facility: Unite Hemopathies Lymphoides Hospital Henri Mondor
state: Ile-de-France
city: Nantes
country: France
facility: CHU Hotel Dieu Service Hematologie
state: Loire
city: Pierre-Benite
country: France
facility: Hopital Lyon Sud
state: Lyon
city: Lille
country: France
facility: Hopital Claude Huriez - CHR Lille
state: Nord
city: Poitiers
country: France
facility: Chu Poitiers - Pole Regional De Cancerologie
state: Vienne
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hospital de la Pitie-Salpetriere
city: Villingen-Schwenningen
country: Germany
facility: Klinik fur Innere Medizin II - Schwarzwald Baar Klinikum
state: Donaueschingen
city: Mutlangen
country: Germany
facility: Kliniken Ostalb Stauferklinikum Schwab Gmund
state: Gmund
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Halle Saale
country: Germany
facility: University Hospital Halle Saale
city: Wurzburg
country: Germany
facility: Universitatsklinik Wurzburg, Med Klinik und Poliklinik II, Zentrum Innere Medizin
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
state: Foggia
city: Milano
country: Italy
facility: UOC Hematologia, Fondazione IRCCS, Ca Granda, OM Policlinico
state: Milan
city: Bologna
country: Italy
facility: University of Bologna Dipartimento di Medicina Specialistica Diagnostica e Sperimentale
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Livorno
country: Italy
facility: Uos Ematologia - Ospedale Civile di Livorno
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Division of Hematology
city: Novara
country: Italy
facility: AOU Maggiore della Carita
city: Perugia
country: Italy
facility: Presidio Ospedaliero Santa Maria della Misericordia
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria Terni
city: Varese
country: Italy
facility: Ospedale dell'Angelo - Varese
city: Venice
country: Italy
facility: Ospedale DellAngelo Di Mestre
city: Nagoya
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
state: Aichi
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aiti
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba-ken
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization National Kyushu Cancer Center
state: Hukuoka
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Isehara-Shi
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Kyoto City
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
state: Kyoto
city: Osaka City
country: Japan
facility: Osaka Metropolitan University Hospital
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Chiba-shi
country: Japan
facility: Chiba Cancer Center
state: Tiba
city: Chuo ku
country: Japan
facility: National Cancer Center Hospital - Tsukiji Campus
state: Tokyo
city: Yamagata City
country: Japan
facility: Yamagata University Hospital
state: Yamagata Prefecture
city: Nagasaki
country: Japan
facility: Japanese Red Cross Nagasaki Genbaku Hospital
city: Daegu si
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
state: Daegu
city: Ulsan
country: Korea, Republic of
facility: University of Ulsan College of Medicine
state: Daegu
city: Gyeonggi do
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Gyeonggi
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital - Hemato Oncology
city: Krakow
country: Poland
facility: Matopolskie Centrum Medyczne S.C.
state: Malopolskie
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im M Sklodowskiej CurieOddzial Chorob United Kingdomladu Chlonnego
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum
state: Pomorskie
city: Gdynia
country: Poland
facility: Pomorskie Hospitals SP. Z O. O. Oncology And Radiotherapy Ward
state: Pomorskie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gdynia
country: Poland
facility: Szpitale Pomorskie spSp. Z.o.o.
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika w Lodzi (Copernicus Memorial Hospital)
city: Warszawa
country: Poland
facility: Instytut Hematologii I Transfuzjologii Klinika Hematologii
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny we Wroclawiu, Klinika Hematologii, Terapii Komorkowych i Chorob Wewnetrznych
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Raffles Cancer Centre
city: Singapore
country: Singapore
facility: Icon Soc Farrer Park
city: Palma
country: Spain
facility: Hospital Universitari Son Espases
state: Balearic Islands
city: Barcelona
country: Spain
facility: Ico Lhospitalet - Hospital Duran i Reynals
state: Catalonia
city: Donostia
country: Spain
facility: Hospital Universitario Donostia
state: Gipuzkoa
city: Palma
country: Spain
facility: Hospital Son Llatzer
state: Illes Balears
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Salud Madrid
state: Madrid
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona - Planta 4 Escalera
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: MD Anderson Cancer Center- Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital Kaohsiung
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Taichung City
country: Taiwan
facility: China Medical University
city: Tainan City
country: Taiwan
facility: National Cheng Kung University
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Center - Liuying
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei City
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Plymouth
country: United Kingdom
facility: Derriford Hospital and the Royal Eye Infirmary
state: Devon
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
state: Surrey
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: