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3097 A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma (Glo-BNHL)

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Antibody Therapy, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Non-Biological therapies, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Chemotherapy, Combination therapy, pediatric, Diseases, Therapies, Lymphoid Malignancies, young adult , Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Emma Seaford1*, Shanna Maycock, MSc2*, Sarah Alexander, MD3*, Auke Beishuizen, MD, PhD4, Birte Wistinghausen, MD5, Veronique Minard-Colin, MD, PhD6*, Charlotte Rigaud, MD6*, Charles A Phillips, MD7*, James B. Ford, DO8, Pamela R. Kearns, PhD, FRCPC2*, Anna Lawson, BSc2*, Ellie Williams9*, Zahra Ahmed2*, Mahnoor Muzaffar2*, Rhianna Parsons2*, Lia Gore, MD10,11, Nicole Scobie12*, Victoria Buenger13*, Carl Allen14*, Karin Mellgren15*, Catherine M. Bollard, MD5, Anne Auperin6*, Lucinda Billingham2* and Gladstone Austin Amos Burke, MB, PhD16*

1University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom
2Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
3The Hospital For Sick Children, Toronto, ON, CAN
4Princess Máxima Center For Pediatric Oncology, Utrecht, NLD
5Children’s National Hospital, Washington, DC
6Gustave Roussy, Villejuif, France
7Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA
8University of Nebraska Medical Center, Omaha, NE
9Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, ENG, United Kingdom
10Children's Hospital Colorado, Aurora, CO
11Center for Cancer and Blood Disorders, University of Colorado Cancer Center, Aurora, CO
12Zoé4life, Sullens, Switzerland
13Coalition Against Cancer, Philadelphia, PA
14Texas Children's Cancer Center, Houston, TX
15Queen Silvia Children’s Hospital, Gothenburg, SWE
16Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom


Glo-BNHL is an adaptive prospective international academic-led multicentre platform clinical trial designed to evaluate the efficacy and safety of the most promising novel agents as monotherapy or in combination with existing therapies for the treatment of children, adolescents, and young adults with relapsed or refractory (r/r) B-cell Non-Hodgkin Lymphoma (B-NHL). A direct output of the second ACCELERATE multi-stakeholder Paediatric Strategy Forum (Pearson, 2019), Glo-BNHL was designed in collaboration with patient advocates, is supported by the Regulatory Authorities, and the intent is for trial data to support filing for marketing authorisation.


Outcomes for r/r paediatric B-NHL are extremely poor with long term cure rates lower than 30%. Glo-BNHL fulfils the critical need for a single collaborative global approach to find new treatments for these rare patients for whom current therapy is inadequate. It allows for a rational approach to investigating the array of potentially promising agents currently in development for adults.

The classes of agents currently prioritised for inclusion in Glo-BNHL are:

  • Treatment Arm I: bispecific antibodies (BsAbs)
  • Treatment Arm II: antibody-drug conjugates (ADCs) combined with standard chemotherapy
  • Treatment Arm III: chimeric antigen receptor (CAR) T-cell products

A robust systematic assessment of each asset is undertaken before a decision to include in the platform is made (published separately).


Glo-BNHL will enrol participants in ≥45 sites in 18 countries spanning Europe, Asia, North America and Australasia. Eligible patients are aged ≤25 years with radiologically or histologically proven relapsed (≥ first) or refractory B-NHL with evaluable disease, adequate organ function, negative pregnancy test, agreement to use effective contraception and written informed consent. Key exclusion criteria include recent stem cell transplant, craniospinal radiation or investigational treatment, on-going moderate or severe acute toxicities, uncontrolled infection or primary immunodeficiency. Patients may be enrolled into any of the available treatment arms for which they are eligible.

Statistical Design

In this rare population we anticipate global enrolment of 30 patients per year. The Bayesian design enables initial cohorts of 15 patients to be meaningfully evaluated. A transition analysis will estimate with ≥80% certainty whether the true efficacy of the treatment exceeds the pre-defined target response rate. Agents demonstrating sufficient promise will be further evaluated in an expansion stage, following discussion with regulators to clarify data requirements to enable subsequent approval of the agent. Confirmatory analyses of all evaluable patients will estimate with ≥95% certainty whether the true efficacy exceeds the target response rate (“GO”). During both initial and expansion stages patients will be closely monitored, with regular interim futility analyses employed, allowing a treatment arm to stop early if there is very little probability of efficacy (“NoGO”).

Outcome measures

Primary outcomes measures are occurrence of an objective response after 12 weeks of treatment (Treatment Arm I), occurrence of complete response within a maximum of three cycles of treatment (Treatment Arm II) and occurrence of an objective response following CAR T-cell infusion (Treatment Arm III). Secondary outcome measures include event-free survival, progression-free survival, overall survival time, best overall response, duration of response, adverse events, pharmacokinetic profile and pharmacodynamics markers.


Treatment Arm I: Odronextamab (Regeneron) – a human CD20xCD3 bispecific antibody – monotherapy will be given as an intravenous infusion weekly for 12 weeks, then at a decreasing frequency until progression or up to two years for responding patients.

Treatment Arm II: Loncastuximab tesirine (ADC Therapeutics) – a humanised CD19-targeting monoclonal antibody with PBD dimer cytotoxin – will be given as an intravenous infusion with each cycle of modified R-ICE chemotherapy (rituximab, ifosfamide, carboplatin, etoposide and dexamethasone) for up to three cycles.

Treatment Arm III: product negotiations are on-going


Glo-BNHL addresses an urgent unmet clinical need through an innovative trial design serving as a paradigm for evaluation of novel agents in very rare diseases.

Disclosures: Minard-Colin: Aztra: Consultancy; BMS: Consultancy; Adaptimmune Therapeutics plc: Consultancy; Roche: Consultancy. Phillips: Merck Group: Consultancy. Gore: Roche: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Allen: Sobi: Consultancy. Bollard: Cabaletta Bio, Catamaran Bio: Current equity holder in private company, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Patent applications in CAR-NKs; Roche: Consultancy. Auperin: MSD France: Consultancy. Burke: Novartis: Consultancy.

*signifies non-member of ASH