B-Cell Non-Hodgkin Lymphoma (B-NHL)
Conditions
Keywords
Non-Hodgkin lymphomas (NHLs), Aggressive NHL, B-Cell Non-Hodgkin Lymphoma (B-NHL), Odronextamab, Anti-CD20 × anti-CD3 bispecific antibody, Relapsed/Refractory NHL
Brief summary
This 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 safe, tolerable and effective the study drug is when given alone. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug versus Standard of Care (SOC) * 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) * Comparing the impact from the study drug versus SOC on quality-of-life and ability to complete routine daily activities
Interventions
DRUGOdronextamab
Administered by intravenous (IV) infusion
DRUGIfosfamide
Administered by IV infusion, as part of the ICE ± R salvage therapy
DRUGCarboplatin
Administered by IV infusion, as part of the ICE ± R salvage therapy
DRUGEtoposide
Administered by IV infusion, as part of the ICE ± R salvage therapy
DRUGRituximab
Administered by IV infusion, as part of the ICE ± R, or DHAP ± R, or GDP ± R salvage therapy.
DRUGDexamethasone
Administered by IV, or orally (PO) as part of the DHAP ± R, or GDP ± R salvage therapy.
DRUGCisplatin
Administered by IV infusion, as part of the DHAP ± R or GDP +/-R salvage therapy.
DRUGCytarabine
Administered by IV infusion, as part of the DHAP ± R salvage therapy.
DRUGGemcitabine
Administered by IV infusion, as part of the GDP ± R salvage therapy.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 Only patients who received 1 prior line of therapy containing an anti-Cluster of Differentiation 20 (CD20) antibody and anthracycline are allowed for enrollment 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), as described in the protocol 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 6. Adequate hematologic and organ function. Key
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 /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival (EFS) as assessed by independent central review (ICR) | Assessed up to 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) as assessed by ICR | Assessed up to 3 years | — |
| Best overall response (BOR) as assessed by ICR | Assessed 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 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 ICR | Assessed up to 6 months | — |
| CR as assessed by local investigator | Assessed up to 6 months | — |
| Duration of response (DOR) assessed by ICR | Assessed up to 3 years | — |
| DOR assessed by local investigator | 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 | — |
| Overall change in patient-reported outcomes (PROs), 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 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) 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). |
Countries
Argentina, Australia, Brazil, Chile, Colombia, Hungary, Malaysia, Romania, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye)
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed