Glo-BNHL: A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

The University Of Birmingham

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Feb 2026 → ongoing

Decision date (initial)

2025-08-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ADC Therapeutics · Fight Kids Cancer · Cancer Research UK · Regeneron Pharmaceuticals

External identifiers

EU CT number

2024-510575-38-00

ClinicalTrials.gov

NCT05991388

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Therapy, Safety

Treatment Arm I: BsAb: Estimate the clinical efficacy of BsAb treatment in patients with relapsed or refractory B-NHL in either first (only one prior line of therapy) or subsequent relapse (more than one prior line of therapy)
Treatment Arm II: ADC with standard chemotherapy: Estimate the clinical efficacy of ADC treatment with modified R-ICE (rituximab, ifosfamide, carboplatin, etoposide and dexamethasone) chemotherapy in patients with relapsed or refractory B-NHL in first (only one prior line of therapy) or subsequent relapse (more than one prior line of therapy)
Treatment Arm III: CAR T-cells: Estimate the efficacy of CAR T-cell therapy in relapsed or refractory BNHL patients who have CAR T-cell product available

Secondary objectives 3

1. Assess the safety profile of the novel agent in children, adolescents and young adults
2. Confirm the pharmacokinetics of the novel agent at the recommended trial dose in children, adolescents and young adults, where relevant
3. Any other treatment arm specific objectives (e.g. assess the relevant pharmacodynamic markers for the novel agent). These will be detailed in the relevant treatment arm sections of the protocol.

Conditions and MedDRA coding

Relapsed and refractory mature B-cell non-Hodgkin Lymphoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003149-PIP01-21, EMEA-002665-PIP02-20

Plan to share IPD

Yes

IPD plan description

The CRCTU is committed to responsible and controlled sharing of anonymised clinical trial data with the wider research community to maximise potential patient benefit while protecting the privacy and confidentiality of trial participants. Data anonymised in compliance with the Information Commissioners Office requirements, using a procedure based on guidelines from the Medical Research Council (MRC) Methodology Hubs and Information Commissioners Office, will be available for sharing with researchers outside of the trials team within 6 months of the primary publication.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Histologically proven mature high-grade B-NHL classified according to either: o the 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 the 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
2. Written informed consent given by patient and/or parents/legal representative
3. 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
4. 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
5. 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)
6. Treatment Arm I: Adequate hepatic function documented by: o Alanine 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 Total bilirubin ≤1.5 x ULN  Patients with known Gilbert syndrome will be excluded if the total bilirubin value is >4 x ULN for the local general population
7. 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
8. 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)
9. Treatment Arm II: Adequate hepatic function documented by: o Alanine 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 Alkaline phosphatase (ALP) ≤ 2.5 x ULN (<5 x ULN if attributed to lymphoma infiltration of liver) o Total bilirubin ≤1.5 x ULN  Patients with known Gilbert syndrome will be excluded if the total bilirubin value is >4 x ULN for the local general population
10. 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 Relapsed 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 Relapsed disease occurring more than two years after previous therapy; biopsy required to confirm relapsed disease o Relapsed or refractory disease following previous therapy within the Glo-BNHL platform; biopsy required to confirm relapsed disease o Partial Response (PR) to previous therapy; biopsy required to confirm active residual disease
11. Evaluable disease as per the Revised International Paediatric Non-Hodgkin Lymphoma Staging System (Appendix 9), including: o at least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest dimension; o or 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 or 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 or, dependent on treatment arm, evaluable Central Nervous System (CNS) only disease (evaluable by imaging or Cerebrospinal Fluid (CSF) analysis)
12. Aged from birth to ≤25 years old at the time of trial entry
13. Performance status ≥50 using Karnofsky or Lansky performance scores
14. Life expectancy of ≥8 weeks
15. Adequate bone marrow function documented by: o Platelet count ≥50 x 10^9/L (no platelet transfusion therapy within seven days prior to treatment) unless bone marrow involvement o Absolute neutrophil count (ANC) ≥0.75 x 10^9/L (no granulocyte colony stimulating factor within 2 days prior to treatment) unless bone marrow involvement
16. Documented negative pregnancy test for female patients of childbearing potential within seven days prior to trial entry
17. Patients of reproductive potential must agree to use effective contraception whilst on trial treatment and for 12 months following treatment discontinuation. - o 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 (see Appendix 2 for details).
18. Patients of reproductive potential must agree not to donate sperm or eggs whilst on trial treatment and for 12 months following treatment discontinuation

Exclusion criteria 27

1. B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
2. Patients with post-transplant lymphoproliferative disorder (PTLD)
3. Patients with primary CNS lymphoma
4. Patients within: o 90 days after an allogenic HSCT procedure o 45 days after an autologous HSCT procedure o Patients within 28 days of systemic therapy and/or immunosuppressive treatment for Graft versus Host Disease (GvHD) o 14 days of previous investigational treatment o 28 days of receiving craniospinal radiation, unless otherwise specified in the treatment arm specific eligibility criteria; or 14 days of any other radiation
5. Patients who have ongoing acute toxicities from most recent lymphoma directed therapy (any toxicity ≥ grade 3 not otherwise defined in the exclusion criteria)
6. Patients who have received any cytoreductive or other chemotherapy in the last 7 days prior to trial entry
7. Patients with known DNA repair disorder or known primary immunodeficiency
8. Patients who are pregnant or breastfeeding (exclusively or partially)
9. 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
10. Uncontrolled concomitant infection. Severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of trial entry
11. Known HIV positivity
12. 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 Unimmunized and HBsAg and/or anti-HBs antibody and/or anti-HBc antibody positive, or o Immunized and HBsAg and/or anti-HBc antibody positive
13. Live vaccine within 28 days prior to trial entry
14. Known history of hypersensitivity to any of the treatments or excipients
15. Treatment Arm I: Central Nervous System (CNS) only disease
16. Treatment Arm I: Patients within 28 days of any CAR-T cell therapy or other cellular therapies
17. Treatment Arm I: Patients within 90 days of receiving craniospinal irradiation
18. 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
19. Treatment Arm I: Known CD20 negative disease at initial diagnosis
20. Treatment Arm I: Seizure within the last 12 months
21. Treatment Arm I: Prior treatment with CD20 x CD3 bispecific therapy
22. Treatment Arm I: Known hypersensitivity to both allopurinol and rasburicase
23. Treatment Arm II: Patients aged <6 months old at the time of trial entry
24. Treatment Arm II: Patients within 42 days of any CAR-T cell therapy or other cellular therapies
25. 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)
26. Treatment Arm II: Steroid treatment for more than a total of seven days in the 14 days prior to trial entry
27. Treatment Arm II: Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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)
2. 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)

Secondary endpoints 10

1. Event-free survival time (EFS)
2. Progression-free survival time (PFS)
3. Overall survival time (OS)
4. Best overall response (BOR) during treatment
5. Duration of response (DOR)
6. Occurrence of an objective response (OR), where relevant
7. Occurrence of adverse events of special interest (AESI)
8. Occurrence of treatment emergent adverse events (TEAEs), where relevant
9. Pharmacokinetic profile of novel agent, where relevant
10. Pharmacodynamic markers, where relevant

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 14

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

The University Of Birmingham

Sponsor organisation

The University Of Birmingham

Address

Vincent Drive

City

Birmingham

Postcode

B15 2TT

Country

United Kingdom

Scientific contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Public contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Third parties 8

Locations

6 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 107 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications