NCT05991388

Brief Summary

The Glo-BNHL trial is trying to find better medicines for children and young people with B-cell non-Hodgkin Lymphoma (B-NHL) that does not go away (refractory B-NHL) or does but comes back again (relapsed B-NHL). B-NHL is a type of cancer that develops inside or outside of lymph nodes (glands) and organs such as the liver or spleen. Examples of B-NHL are Burkitt Lymphoma and Diffuse Large B Cell Lymphoma, which may be other names used to describe this type of cancer. It is very difficult to cure relapsed or refractory B-NHL. The medicines used now are very powerful with many side effects and only cure around 30 in every 100 children treated. It is very important that investigators quickly find better medicines for these children and young people. The Glo-BNHL trial will include three groups of children and young people, each given a new medicine (either alone or with chemotherapy). The investigators are looking to make sure the new medicines are safe and that they work to treat the cancer. If the medicine in one group does not work for a child in the trial, then they may be able to join a different group to have another new medicine. Experts from around the world will carefully pick the medicines most likely to be helpful to be part of the trial. If one of the new medicines seems not to be working as well as hoped then the investigators will take it out of the trial as soon as possible. This will let other new medicines be added to the trial and tested. If a medicine does seem to be working well, then it will continue in the trial to make sure it really is the most useful medicine available. Children from around the world will be invited to take part in the trial. The investigators will then check on them for at least two years after they finish the trial treatment to look for possible side effects of the new medicine.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
210

participants targeted

Target at P75+ for phase_2

Timeline
85mo left

Started May 2024

Longer than P75 for phase_2

Geographic Reach
6 countries

8 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress22%
May 2024May 2033

First Submitted

Initial submission to the registry

July 24, 2023

Completed
21 days until next milestone

First Posted

Study publicly available on registry

August 14, 2023

Completed
9 months until next milestone

Study Start

First participant enrolled

May 2, 2024

Completed
7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2031

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2033

Last Updated

February 20, 2026

Status Verified

February 1, 2026

Enrollment Period

7 years

First QC Date

July 24, 2023

Last Update Submit

February 18, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • Treatment Arm I: BsAb: Occurrence of an objective response (OR)

    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)

    At the end of week 12 of treatment

  • Treatment Arm II: ADC with standard chemotherapy: Occurrence of CR

    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)

    At the end of Cycle 2 and Cycle 3 of treatment (each cycle is 28 days)

Secondary Outcomes (8)

  • Event-free survival time (EFS)

    From start of treatment until last patient has been followed up for 2 years

  • Progression-free survival time (PFS)

    From start of treatment until last patient has been followed up for 2 years

  • Overall survival time (OS)

    From start of treatment until last patient has been followed up for 2 years

  • Best overall response (BOR) during treatment

    At the end of weeks 4, 8, and 12 for Treatment Arm I; at the end of cycles 1, 2, and 3 for Treatment Arm II (each cycle is 28 days)

  • Duration of response (DOR)

    From start of treatment until last patient has been followed up for 2 years

  • +3 more secondary outcomes

Study Arms (3)

Treatment Arm I - BsAb - Odronextamab

EXPERIMENTAL

Patients will receive odronextamab given as an intravenous infusion weekly for 12 weeks, then every two weeks until nine months, and every four weeks thereafter until progression or for a maximum of two years

Drug: Odronextamab

Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

EXPERIMENTAL

Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles)

Drug: Loncastuximab tesirineDrug: RituximabDrug: IfosfamideDrug: CarboplatinDrug: EtoposideDrug: Etoposide PhosphateDrug: Dexamethasone

Treatment Arm III - CAR T-cells - TBC

EXPERIMENTAL

Patients will receive CAR-T cell therapy - agent TBC

Biological: CAR T-cells (TBC)

Interventions

Modified R-ICE (Treatment Arm II)

Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

Modified R-ICE chemotherapy

Treatment Arm III - CAR T-cells - TBC

CD20xCD3 bispecific antibody

Also known as: REGN-1979
Treatment Arm I - BsAb - Odronextamab

CD-19-directed antibody-drug conjugate

Also known as: ADCT-402
Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

Modified R-ICE chemotherapy

Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

Modified R-ICE chemotherapy

Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

Modified R-ICE chemotherapy

Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

Modified R-ICE chemotherapy

Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

Modified R-ICE chemotherapy

Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE

Eligibility Criteria

AgeUp to 25 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Histologically proven mature B-NHL (Diffuse Large B-Cell Lymphoma (DLBCL), Burkitt Lymphoma/Leukaemia or atypical Burkitt/Burkitt-like lymphoma, primary mediastinal large B-cell lymphoma (PMLBL), and mature B-NHL/Not Otherwise Specified (NOS)) at initial diagnosis
  • 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. (Note: relapses following prior targeted therapy must have continuing target positivity, confirmed by an established method).
  • If relapse occurs more than two years after previous therapy, a biopsy must be performed
  • Evaluable disease as per the international paediatric non-Hodgkin Lymphoma response criteria, including:
  • at least one bi-dimensionally measurable nodal lesion \>1.5 cm in its longest dimension;
  • 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);
  • 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);
  • or, dependent on treatment arm, evaluable Central Nervous System (CNS) only disease (evaluable by imaging or Cerebrospinal Fluid (CSF) analysis)(\*\*)
  • Age from birth to ≤25 years old at the time of trial entry
  • Performance status ≥50 using Karnofsky or Lansky performance scores
  • Life expectancy of ≥8 weeks
  • Adequate bone marrow function documented by:
  • Platelet count ≥50x 10\^9/L (no platelet transfusion therapy within seven days prior to treatment) unless bone marrow involvement(\*\*\*)
  • 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(\*\*\*)
  • Adequate hepatic function documented by:
  • +20 more criteria

You may not qualify if:

  • B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
  • Patients within:
  • days after an allogenic HSCT procedure
  • days after an autologous HSCT procedure
  • days of experiencing graft versus host disease (GvHD) requiring systemic therapy, and/or immunosuppressive treatment
  • days of previous investigational treatment
  • days of receiving craniospinal radiation; or 14 days of any other radiation
  • For patients who have received any CAR T-cell therapy or other cellular therapies, see treatment arm specific eligibility criteria
  • Patients who have ongoing acute toxicities from most recent lymphoma directed therapy
  • Patients with known DNA repair disorder or known primary immunodeficiency
  • Patients who are pregnant or breastfeeding (exclusively or partially)
  • Patients who cannot regularly be followed up in accordance with the protocol due to psychological, social, geographical or other issues
  • Patients for whom non-compliance with treatment or trial procedures is expected
  • Uncontrolled concomitant infection. Severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of trial entry
  • Known HIV positivity
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

The Children's Hospital at Westmead

Sydney, New South Wales, Australia

NOT YET RECRUITING

Queensland Children's Hospital

Brisbane, Queensland, Australia

NOT YET RECRUITING

Perth Children's Hospital

Perth, Washington, Australia

RECRUITING

St. Anna Children's Hospital

Vienna, Austria

RECRUITING

UZ Leuven

Leuven, Belgium

NOT YET RECRUITING

Princess Máxima Centre for Pediatric Oncology

Utrecht, Netherlands

RECRUITING

Starship Children's Hospital

Auckland, New Zealand

NOT YET RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

NOT YET RECRUITING

Birmingham Children's Hospital

Birmingham, United Kingdom

RECRUITING

Bristol Royal Hospital for Children

Bristol, United Kingdom

RECRUITING

Royal Manchester Children's Hospital

Manchester, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

loncastuximab tesirineRituximabIfosfamideCarboplatinEtoposideetoposide phosphateDexamethasoneImmunotherapy, AdoptiveTubercidin

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCyclophosphamidePhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsOxazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCoordination ComplexesPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsSteroids, FluorinatedAdoptive TransferImmunization, PassiveImmunizationImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative TechniquesPurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Study Officials

  • Amos Burke

    University of Birmingham

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Platform trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 24, 2023

First Posted

August 14, 2023

Study Start

May 2, 2024

Primary Completion (Estimated)

May 1, 2031

Study Completion (Estimated)

May 1, 2033

Last Updated

February 20, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations