A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma
- Conditions
- B-Cell Non-Hodgkin Lymphoma (B-NHL)
- Interventions
- Registration Number
- NCT06230224
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on patients with previously treated aggressive B-cell non-Hodgkin lymphoma whose cancer has stopped responding to treatment (also known as 'refractory') or has returned (also known as 'relapsed'). The aim of the study is to see how effective the study drug is compared to standard of care (SOC) therapy.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug versus SOC
* How much study drug is in your blood at different times
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
* Comparing the impact from the study drug versus SOC on your quality-of-life and ability to complete routine daily activities
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 216
-
Histologically proven aggressive B-NHL, as described in the protocol. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed.
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Have primary refractory or relapse 12 months or less from initiation of frontline therapy.
Treatment at frontline should have included anti-cluster of differentiation 20 (anti-CD20) antibody and anthracycline-containing regimen.
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Have measurable disease with at least one nodal lesion with longer diameter (LDi) greater than 1.5 cm or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]).
-
Intent to proceed to autologous stem cell transplant (ASCT).
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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Adequate hematologic and organ function.
- Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol.
- History of or current relevant CNS pathology, as described in the protocol.
- A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated.
- Any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol.
- Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol.
- Allergy/hypersensitivity to study drug, or excipients.
NOTE: Other protocol defined inclusion / exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Odronextamab Odronextamab Participants will receive odronextamab monotherapy. Standard Of Care Ifosfamide Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR). Standard Of Care Cisplatin Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR). Standard Of Care Rituximab Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR). Standard Of Care Dexamethasone Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR). Standard Of Care Cytarabine Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR). Standard Of Care Gemcitabine Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR). Standard Of Care Etoposide Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR). Standard Of Care Carboplatin Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab \[ICE ± R\], or dexamethasone, cisplatin, cytarabine ± rituximab \[DHAP ± R\], or gemcitabine, dexamethasone, cisplatin ± rituximab \[GDP ± R\]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR).
- Primary Outcome Measures
Name Time Method Event-free survival (EFS) as assessed by independent central review Assessed up to 3 years
- Secondary Outcome Measures
Name Time Method Progression free survival (PFS) as assessed by independent central review Assessed up to 3 years Best overall response (BOR) as assessed by independent central review Assessed up to 6 months Overall change in physical functioning as measured by scores of the physical function scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) Assessed up to 3 years The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a global health status (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.
EFS as assessed by local investigator Assessed up to 3 years PFS as assessed by local investigator Assessed up to 3 years BOR as assessed by local investigator Assessed up to 6 months Complete response (CR) as assessed by independent central review Assessed up to 6 months CR as assessed by local investigator Assessed up to 6 months Duration of response (DOR) assessed by independent central review Assessed up to 3 years DOR assessed by local investigator Assessed up to 3 years Overall survival (OS) Assessed up to 3 years Incidence of treatment-emergent adverse events (TEAEs) Assessed up to 1 year Severity of TEAEs Assessed up to 1 year Odronextamab concentrations in serum Assessed up to 6 months Incidence of anti-drug antibodies (ADAs) to odronextamab over the study duration Assessed up to 6 months Titers of ADAs to odronextamab over the study duration Assessed up to 6 months Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration Assessed up to 6 months Measurable residual disease (MRD) status Assessed up to 6 months Duration of MRD-negativity, as determined by circulating tumor DNA (ctDNA) Assessed up to 3 years Overall change in patient-reported outcomes, as measured by scores of the EORTCQLQ- C30 Assessed up to 3 years 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.
Overall change in patient-reported outcomes, as measured by scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS) Assessed up to 3 years 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.
Overall change in patient-reported outcomes, as measured by scores of the EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L) Assessed up to 3 years 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".
Overall change in score of the Global Population item 5 (GP5) of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire Assessed up to 3 years 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 (61)
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Fundacion Jimenez Diaz University Hospital
🇪🇸Madrid, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
University Hospital Doctor Peset
🇪🇸Valencia, Spain
Chang Gung Medical Foundation
🇨🇳Chiayi City, Chianan Plain, Taiwan
Changhua Christian Hospital
🇨🇳Changhua City, Taiwan
Chang Gung Memorial Hospital Kaohsiung
🇨🇳Kaohsiung City, Taiwan
Taipei Medical University - Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan
Taichung General Veterans Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Tri-Service General Hospital
🇨🇳Taipei City, Taiwan
Chulalongkorn University
🇹🇭Bangkok, Thailand
Sriraj Hospital
🇹🇭Bangkok, Thailand
Chiang Mai University
🇹🇭Chiang Mai, Thailand
Khon Kaen University
🇹🇭Khon Kaen, Thailand
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Gyeongsangnam-do, Korea, Republic of
Chang Gung Memorial Hospital - Linkou Branch
🇨🇳Taoyuan, Hunan Province, Taiwan
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Olivia Newton John Cancer Wellness & Research Centre
🇦🇺Heidelberg, Victoria, Australia
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Forli Cesena, Italy
Centro Di Riferimento Oncologico (CRO), Aviano, National Cancer Institute
🇮🇹Aviano, Province Of Pordenone, Italy
Azienda Ospedaliera Spedali Civili di Brescia
🇮🇹Brescia, Italy
AOU Maggiore della Carita
🇮🇹Novara, Italy
Ospedale di Circolo e Fondazione Macchi Varese
🇮🇹Varese, 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
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
Jeonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Yeouido St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Gazi University
🇹🇷Ankara, Central Anatolia, Turkey
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Hospital Sultanah Aminah Jhor Bahru
🇲🇾Johor Bahru, Johor, Malaysia
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Sabah, Malaysia
Hospital Ampang
🇲🇾Kuala Lumpur, Selangor, Malaysia
Subang Jaya Medical Center
🇲🇾Subang Jaya, Selangor, Malaysia
VM Medical Park Mersin Hospital
🇹🇷Mezitli, Mersin, Turkey
Tekirdag Namik Kemal University Hospital
🇹🇷Tekirdag, Suleymanpasa, Turkey
Sbu Dr.A.Y. Ankara Onkoloji Suam
🇹🇷Ankara, Turkey
Ege University
🇹🇷Izmir, Turkey
Sakarya University Medical Faculty
🇹🇷Sakarya, Turkey
Ondokuz Mayıs University
🇹🇷Samsun, Turkey
Zonguldak Bulent Ecevit Univesity
🇹🇷Zonguldak, Turkey
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia
Erasmus University Medical Center
🇳🇱Rotterdam, Netherlands
National University Hospital Singapore
🇸🇬Singapore, Singapore
Singapore General Hospital
🇸🇬Singapore, Singapore
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Andalusia, Spain
Hospital Universitari Son Espases
🇪🇸Palma, Balearic Islands, Spain
Hospital Universitari Mutua Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Virgen De Las Nieves De Granada
🇪🇸Granada, Spain