Assess the anti-tumor activity and safety of odronextamab in patients with relapsed or refractory B-cell non-Hodgkin Lymphoma

JRCT ID: jRCT2031210617

Registered date:18/02/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsed or refractory B-cell non-Hodgkin Lymphoma
• Date of first enrollment: 27/07/2022
• Target sample size: 40
• Countries of recruitment: Australia,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Italy,Japan,South Korea,Japan,Poland,Japan,Singapore,Japan,Spain,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Odronextamab
Administered by intravenous (IV) infusion
Other Name: REGN1979

Outcome(s)

Primary Outcome

1.ORR (FL grade 1-3a/MZL) [ Time Frame: From first patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study]
According to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review.
2.ORR (DLBCL/MCL/Other B-NHL) [ Time Frame: From first patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study]
According to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review.

Secondary Outcome

- ORR (FL/MZL) [ Time Frame: First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study. ]
According to the Lugano Classification, as assessed by local investigator evaluation
- ORR (DLBCL/MCL/Other B-NHL) [ Time Frame: First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study. ]
According to the Lugano Classification, as assessed by local investigator evaluation
- CR rate (FL grade 1-3a/MZL) [ Time Frame: First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study. ]
According to the Lugano Classification and as assessed by local investigator evaluation and independent central review
- CR rate (DLBCL/MCL/Other B-NHL) [ Time Frame: First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study. ]
According to the Lugano Classification and as assessed by local investigator evaluation and independent central review
- PFS [ Time Frame: First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose ]
According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
- OS [ Time Frame: First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose]
- DOR [ Time Frame: First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose]
According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
- DCR (FL grade 1-3a/MZL) [ Time Frame: First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.]
According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
- DCR (DLBCL/MCL/Other B-NHL) [ Time Frame: First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.]
According to the Lugano Classification and as assessed by independent central review and local investigator evaluation
- Incidence and severity of treatment emergent adverse events (TEAEs) [ Time Frame: First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose]
- Pharmacokinetics: Concentration of odronextamab [ Time Frame: 12 weeks following end of treatment]
(End of infusion [EOI]; Concentration at a specified time t [Ct])
- Immunogenicity: Anti-odronextamab antibodies [ Time Frame: 12 weeks following end of treatment]
- Changes in scores of patient-reported outcomes as measured by EORTC QLQ-C30 [ Time Frame: First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose]
- 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).
- Changes in scores of patient-reported outcomes as measured by FACT-Lym [ Time Frame: First patient first dose to disease progression or death due to any cause, whichever comes first, 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 EQ-5D-3L [ Time Frame: First patient first dose to disease progression or death due to any cause, whichever comes first, 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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 that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol
3. 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
4. MCL after BTK inhibitor therapy cohort: New enrollment is paused until further notice
5. MZL cohort: New enrollment is paused until further notice
6. 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.
7. Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment
8. Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI))
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
10. Adequate bone marrow, hepatic, and renal function as defined in the protocol

Exclude 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. Prior treatment with any chimeric antigen receptor T-cell (CAR-T) therapy
5. 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
6. History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded
7. 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.
8. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or other uncontrolled infection as defined in the protocol
9. Known hypersensitivity to both allopurinol and rasburicase
10. Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy
Note: Other protocol-defined Inclusion/Exclusion criteria apply for NCT03888105

Related Information

• Primary Sponsor: Srikanth R. Ambati
• Secondary ID(s): NCT03888105,2017-002139-41