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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

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
Inclusion Criteria
  1. 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.

  2. 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.

  3. 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]).

  4. Intent to proceed to autologous stem cell transplant (ASCT).

  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

  6. Adequate hematologic and organ function.

Exclusion Criteria
  1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol.
  2. History of or current relevant CNS pathology, as described in the protocol.
  3. 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.
  4. 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.
  5. Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol.
  6. 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
GroupInterventionDescription
OdronextamabOdronextamabParticipants will receive odronextamab monotherapy.
Standard Of CareIfosfamideParticipants 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 CareCisplatinParticipants 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 CareRituximabParticipants 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 CareDexamethasoneParticipants 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 CareCytarabineParticipants 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 CareGemcitabineParticipants 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 CareEtoposideParticipants 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 CareCarboplatinParticipants 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
NameTimeMethod
Event-free survival (EFS) as assessed by independent central review (ICR)Assessed up to 3 years
Secondary Outcome Measures
NameTimeMethod
Progression free survival (PFS) as assessed by ICRAssessed up to 3 years
Best overall response (BOR) as assessed by ICRAssessed up to 6 months
Overall survival (OS)Assessed up to 3 years
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 investigatorAssessed up to 3 years
PFS as assessed by local investigatorAssessed up to 3 years
BOR as assessed by local investigatorAssessed up to 6 months
Complete response (CR) as assessed by ICRAssessed up to 6 months
CR as assessed by local investigatorAssessed up to 6 months
Duration of response (DOR) assessed by ICRAssessed up to 3 years
DOR assessed by local investigatorAssessed up to 3 years
Incidence of treatment-emergent adverse events (TEAEs)Assessed up to 1 year
Severity of TEAEsAssessed up to 1 year
Odronextamab concentrations in serumAssessed up to 6 months
Incidence of anti-drug antibodies (ADAs) to odronextamab over the study durationAssessed up to 6 months
Titers of ADAs to odronextamab over the study durationAssessed up to 6 months
Incidence of neutralizing antibodies (NAb) to odronextamab over the study durationAssessed up to 6 months
Measurable residual disease (MRD) statusAssessed up to 6 months
Overall change in patient-reported outcomes (PROs), as measured by scores of the EORTCQLQ- C30Assessed 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 PROs, 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 PROs, 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) questionnaireAssessed 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 (75)

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Queensland, Australia

Royal Hobart Hospital

🇦🇺

Hobart, Tasmania, Australia

Olivia Newton John Cancer Wellness & Research Centre

🇦🇺

Heidelberg, Victoria, Australia

Hospital Santa Izabel - Santa Casa de Misericordia da Bahia

🇧🇷

Salvador, Bahia, Brazil

Ensino e Terapia de Inovacao Clinica Amo (Etica)

🇧🇷

Salvador, Bahia, Brazil

Hospital Sirio Libanes Brasilia

🇧🇷

Brasilia, Federal District, Brazil

Uopeccan Hospital do Cancer de Cascavel

🇧🇷

Cascavel, Parana, Brazil

Hospital Erasto Gaertner

🇧🇷

Curitiba, Parana, Brazil

Hospital de Clinicas de Porto Alegre

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

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Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia

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