ODRONEXTAMAB for Relapsed and refractory B-cell non-Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Histologically proven mature high-grade B-NHL classified according to either: o\tthe 5th edition of the World Health Organisation (WHO) Classification of Haematolymphoid Tumours (WHO-HAEM5), 2022 (diffuse large B-cell lymphoma - not otherwise specified (DLBCL - NOS), high-grade B-cell lymphoma with MYC and BCL-2 rearrangements, primary mediastinal large B-cell lymphoma, Burkitt’s lymphoma, and high-grade B-cell lymphoma - NOS) at initial diagnosis; or o\tthe revised 4th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, 2017 (diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma/leukaemia or Burkitt-like lymphoma with 11q aberration, primary mediastinal large B-cell lymphoma (PMLBL), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements and high-grade B-cell lymphoma - NOS) at initial diagnosis"}
• {"criterion_text":"- Radiologically and/or histologically proven B-NHL in first relapse (only one prior line of therapy) or subsequent relapse (more than one prior line of therapy) or refractory B-NHL. In the following circumstances biopsy is mandated: o\tRelapsed or refractory disease following previous targeted therapy; biopsy required to confirm continuing target positivity (see individual treatment arms for specific relevant targets), confirmed by immunohistochemistry or flow cytometry o\tRelapsed disease occurring more than two years after previous therapy; biopsy required to confirm relapsed disease o\tRelapsed or refractory disease following previous therapy within the Glo-BNHL platform; biopsy required to confirm relapsed disease o\tPartial Response (PR) to previous therapy; biopsy required to confirm active residual disease"}
• {"criterion_text":"- Evaluable disease as per the Revised International Paediatric Non-Hodgkin Lymphoma Staging System (Appendix 9), including: o\tat least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest dimension; o\tor at least one bi-dimensionally measurable extra-nodal lesion >1.0 cm in its longest dimension on computerised tomography (CT) or Magnetic Resonance Imaging (MRI); o\tor bone marrow involvement (≥25% involvement from bone marrow, if only site of disease. Any standard method of assessment is acceptable i.e. cytomorphology, flow cytometry and/or immunohistochemistry); o\tor, dependent on treatment arm, evaluable Central Nervous System (CNS) only disease (evaluable by imaging or Cerebrospinal Fluid (CSF) analysis)"}
• {"criterion_text":"- Aged from birth to ≤25 years old at the time of trial entry"}
• {"criterion_text":"- Performance status ≥50 using Karnofsky or Lansky performance scores"}
• {"criterion_text":"- Life expectancy of ≥8 weeks"}
• {"criterion_text":"- Adequate bone marrow function documented by: o\tPlatelet count ≥50 x 10^9/L (no platelet transfusion therapy within seven days prior to treatment) unless bone marrow involvement o\tAbsolute neutrophil count (ANC) ≥0.75 x 10^9/L (no granulocyte colony stimulating factor within 2 days prior to treatment) unless bone marrow involvement"}
• {"criterion_text":"- Documented negative pregnancy test for female patients of childbearing potential within seven days prior to trial entry"}
• {"criterion_text":"- Patients of reproductive potential must agree to use effective contraception whilst on trial treatment and for 12 months following treatment discontinuation. - o\tPatients of reproductive potential using oral hormonal contraception must use an additional barrier method such as condoms whilst on trial treatment and for 12 months following treatment discontinuation (see Appendix 2 for details)."}
• {"criterion_text":"- Patients of reproductive potential must agree not to donate sperm or eggs whilst on trial treatment and for 12 months following treatment discontinuation"}
• {"criterion_text":"- Written informed consent given by patient and/or parents/legal representative"}
• {"criterion_text":"- Treatment Arm I: Patients of reproductive potential must agree not to donate sperm or eggs whilst on trial treatment and for 6 months following treatment discontinuation"}
• {"criterion_text":"- Treatment Arm I: Patients of reproductive potential using oral hormonal contraception must use an additional barrier method such as condoms whilst on trial treatment and for 12 months following treatment discontinuation"}
• {"criterion_text":"- Treatment Arm I: Adequate renal function, by measured creatinine clearance >45 ml/min (if creatinine levels are normal for the patient’s age, estimated creatinine clearance is sufficient. This must be estimated using the Cockroft-Gault Equation)"}
• {"criterion_text":"- Treatment Arm I: Adequate hepatic function documented by: o\tAlanine aminotransferase (ALT) ≤5 x upper limit of normal (ULN); if ALT not measured, aspartate aminotransferase (AST) ≤5 x ULN (ALT or AST <5 x ULN if attributed to lymphoma infiltration of liver) o\tTotal bilirubin ≤1.5 x ULN \tPatients with known Gilbert syndrome will be excluded if the total bilirubin value is >4 x ULN for the local general population"}
• {"criterion_text":"- Treatment Arm I: Patients who have received CAR T-cell therapy or other cellular therapies more than 28 days prior must demonstrate recovery from acute toxicities and have measurable disease"}
• {"criterion_text":"- Treatment Arm II: Adequate renal function, by measured glomerular filtration rate (GFR) >60 ml/min/1.73 m^2 (estimated GFR may alternatively be used, but must be based on cystatin C)"}
• {"criterion_text":"- Treatment Arm II: Adequate hepatic function documented by: o\tAlanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); if ALT not measured, aspartate aminotransferase (AST) ≤2.5 x ULN (ALT or AST <5 x ULN if attributed to lymphoma infiltration of liver) o\tAlkaline phosphatase (ALP) ≤ 2.5 x ULN (<5 x ULN if attributed to lymphoma infiltration of liver) o\tTotal bilirubin ≤1.5 x ULN \tPatients with known Gilbert syndrome will be excluded if the total bilirubin value is >4 x ULN for the local general population"}

Exclusion criteria

• {"criterion_text":"- B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)"}
• {"criterion_text":"- Uncontrolled concomitant infection. Severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of trial entry"}
• {"criterion_text":"- Known HIV positivity"}
• {"criterion_text":"- Hepatitis B carrier status, history of Hepatitis B Virus or positive serology. A patient is considered as a Hepatitis B Virus carrier or to have (had) Hepatitis B Virus infection in case of: o\tUnimmunized and HBsAg and/or anti-HBs antibody and/or anti-HBc antibody positive, or o\tImmunized and HBsAg and/or anti-HBc antibody positive"}
• {"criterion_text":"- Live vaccine within 28 days prior to trial entry"}
• {"criterion_text":"- Known history of hypersensitivity to any of the treatments or excipients"}
• {"criterion_text":"- Treatment Arm I: Central Nervous System (CNS) only disease"}
• {"criterion_text":"- Treatment Arm I: Patients within 28 days of any CAR-T cell therapy or other cellular therapies"}
• {"criterion_text":"- Treatment Arm I: Patients within 90 days of receiving craniospinal irradiation"}
• {"criterion_text":"- Treatment Arm I: Left ventricular shortening fraction (LVSF) <27% or left ventricular ejection fraction (LVEF) <50%, as determined by ECHO or MUGA, any evidence of pericardial effusion (except trace or physiological) as determined by an ECHO, and any clinically significant arrhythmias"}
• {"criterion_text":"- Treatment Arm I: Known CD20 negative disease at initial diagnosis"}
• {"criterion_text":"- Patients with post-transplant lymphoproliferative disorder (PTLD)"}
• {"criterion_text":"- Treatment Arm I: Seizure within the last 12 months"}
• {"criterion_text":"- Treatment Arm I: Prior treatment with CD20 x CD3 bispecific therapy"}
• {"criterion_text":"- Treatment Arm I: Known hypersensitivity to both allopurinol and rasburicase"}
• {"criterion_text":"- Treatment Arm II: Patients aged <6 months old at the time of trial entry"}
• {"criterion_text":"- Treatment Arm II: Patients within 42 days of any CAR-T cell therapy or other cellular therapies"}
• {"criterion_text":"- Treatment Arm II: Clinically significant (Grade ≥2) third space fluid accumulation (i.e. ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)"}
• {"criterion_text":"- Treatment Arm II: Steroid treatment for more than a total of seven days in the 14 days prior to trial entry"}
• {"criterion_text":"- Treatment Arm II: Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease"}
• {"criterion_text":"- Patients with primary CNS lymphoma"}
• {"criterion_text":"- Patients within: o\t90 days after an allogenic HSCT procedure o\t45 days after an autologous HSCT procedure o\tPatients within 28 days of systemic therapy and/or immunosuppressive treatment for Graft versus Host Disease (GvHD) o\t14 days of previous investigational treatment o\t28 days of receiving craniospinal radiation, unless otherwise specified in the treatment arm specific eligibility criteria; or 14 days of any other radiation"}
• {"criterion_text":"- Patients who have ongoing acute toxicities from most recent lymphoma directed therapy (any toxicity ≥ grade 3 not otherwise defined in the exclusion criteria)"}
• {"criterion_text":"- Patients who have received any cytoreductive or other chemotherapy in the last 7 days prior to trial entry"}
• {"criterion_text":"- Patients with known DNA repair disorder or known primary immunodeficiency"}
• {"criterion_text":"- Patients who are pregnant or breastfeeding (exclusively or partially)"}
• {"criterion_text":"- Patients for whom non-compliance with treatment, trial procedures, or protocol follow up schedule is expected and all available resources to facilitate inclusion have been exhausted"}

Primary endpoints

• {"endpoint_text":"- Treatment Arm I: BsAb: Occurrence of an objective response (OR) i.e. Complete Response (CR) or Partial Response (PR) after 12 weeks of treatment assessed by Independent Central Review (according to International Paediatric Non-Hodgkin Lymphoma Response Criteria)","definition_or_measurement_approach":"Occurrence of CR or PR after 12 weeks assessed by Independent Central Review according to International Paediatric Non-Hodgkin Lymphoma Response Criteria"}
• {"endpoint_text":"- Treatment Arm II: ADC with standard chemotherapy: Occurrence of CR within a maximum of three cycles of treatment assessed by Independent Central Review (according to International Paediatric Non-Hodgkin Lymphoma Response Criteria)","definition_or_measurement_approach":"Occurrence of CR within up to three cycles assessed by Independent Central Review according to International Paediatric Non-Hodgkin Lymphoma Response Criteria"}

Secondary endpoints

• {"endpoint_text":"- Event-free survival time (EFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival time (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival time (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Best overall response (BOR) during treatment","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Occurrence of an objective response (OR), where relevant","definition_or_measurement_approach":""}
• {"endpoint_text":"- Occurrence of adverse events of special interest (AESI)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Occurrence of treatment emergent adverse events (TEAEs), where relevant","definition_or_measurement_approach":""}
• {"endpoint_text":"- Pharmacokinetic profile of novel agent, where relevant","definition_or_measurement_approach":""}
• {"endpoint_text":"- Pharmacodynamic markers, where relevant","definition_or_measurement_approach":""}

Austria

Earliest CTIS Part Ii Submission Date

21-07-2025

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

21

Number Of Sites

1

Number Of Participants

7

Belgium

Earliest CTIS Part Ii Submission Date

15-05-2025

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

88

Number Of Sites

1

Number Of Participants

2

Sweden

Earliest CTIS Part Ii Submission Date

14-07-2025

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

28

Number Of Sites

1

Number Of Participants

7

Netherlands

Earliest CTIS Part Ii Submission Date

30-07-2025

Latest Decision Or Authorization Date

18-08-2025

Processing Time Days

19

Number Of Sites

1

Number Of Participants

7

France

Earliest CTIS Part Ii Submission Date

12-01-2026

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

35

Number Of Sites

3

Number Of Participants

7

Spain

Earliest CTIS Part Ii Submission Date

18-12-2025

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

60

Number Of Sites

3

Number Of Participants

7

Primary sponsor

Full Name

The University Of Birmingham

Organisation Type

Educational Institution

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Premier Research Group Limited

Responsibilities

sponsorDuties codes: ["1"]

Third parties

• {"country":"United Kingdom","full_name":"Premier Research Group Limited","duties_or_roles":"sponsorDuties codes: [\"1\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [\"3\",\"7\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"ADC Therapeutics SA","duties_or_roles":"sponsorDuties codes: [\"14\",\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Prinses Maxima Centrum voor Kinderoncologie B.V.","duties_or_roles":"sponsorDuties codes: [\"15\"] (value: National Coordinating Centre)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Regeneron Pharmaceuticals Inc.","duties_or_roles":"sponsorDuties codes: [\"14\",\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Austria","full_name":"St. Anna Childrens Cancer Research Institute GmbH","duties_or_roles":"sponsorDuties codes: [\"15\"] (value: National Coordinating Centre)","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Sahlgrenska University Hospital-Vaestra Goetalandsregionen","duties_or_roles":"sponsorDuties codes: [\"15\"] (value: National Coordinating Centre)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"UZ Leuven","duties_or_roles":"sponsorDuties codes: [\"15\"] (value: National Coordinating Centre)","organisation_type":"Hospital/Clinic/Other health care facility"}