A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
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.
detailed description
Glo-BNHL is an adaptive prospective international multicentre platform clinical trial designed to evaluate the safety and efficacy of novel agents for the treatment of children, adolescents, and young adults with relapsed and/or refractory B-cell non-Hodgkin Lymphoma (r/r BNHL). The trial is designed to generate sufficient evidence to potentially be practice-changing in this rare cancer setting. With the trial incorporating an initial stage evaluating efficacy followed potentially by an expansion stage to provide confirmatory analysis, the trial could be considered to be phase II/III.
Novel agents will be prioritised for inclusion in the platform according to an overarching prioritisation list and a robust systematic scientific assessment, performed by the international Trial Steering Committee (TSC).
The platform consists of three parallel treatment arms, each one investigating a different novel agent in a group of patients. The platform allows the testing of a pipeline of novel agents in each treatment arm consecutively. Patients in the platform may be enrolled into any of the available treatment arms for which they are eligible. The classes of novel agents prioritised for inclusion at the initiation of the trial are:
* Treatment Arm I: Bispecific antibodies (BsAbs) * Treatment Arm II: Antibody-drug conjugates (ADC) with standard chemotherapy * Treatment Arm III: Chimeric antigen receptor (CAR) T-cells
The platform trial has an adaptive Bayesian design that facilitates efficient GO/NoGO decisions relevant to the target population enrolled in each treatment arm. The Bayesian approach estimates the probability that a novel agent is clinically effective and enables decision-making even with small numbers of patients. It can also incorporate prior knowledge, thereby maximising the utility of all available data in this rare population. It facilitates continuous evaluation of any novel agent as the sample size increases.
Furthermore it allows for the discontinuation of an agent if the observed trial data demonstrate a high probability that the novel agent is ineffective at any time, allowing the next agent in the pipeline to be introduced. If the prioritisation of classes of novel agents by the TSC changes, treatment arms can be amended, added, or removed to reflect this. Not all Treatment Arms will necessarily be open to recruitment at all times.