For patients and the public

The Glo-BNHL trial is trying to find better medicines for children and young people with B-cell Non-Hodgkin’s Lymphoma (B-NHL) that does not go away (refractory B-NHL) or does but then 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. It is very difficult to cure children with relapsed or refractory B-NHL. The medicines used now are very powerful with many side effects and only cure around one in every three children treated. It is very important that we quickly find better medicines for these children.

The Glo-BNHL trial will include three groups of children and young people, each given a new medicine (either alone or with chemotherapy). We 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 we will take it out of the trial. This will let other new medicines be added to the trial to be 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 we have.

Children from around the world will be invited to take part in the trial. We will then check on them for at least two years to look for possible side effects of the new medicine.

• Test the how well new medicines work to improve the outcomes of children, adolescents and young adults with relapsed or refractory B-NHL (alone or combined with existing treatments)
• Test the safety of these new medicines in children, adolescents and young adults with relapsed or refractory B-NHL
• Carry out biological studies to find out how and why some cancers are unaffected by treatment and find possible targets for new medicines

The groups of patients in each treatment arm are as follows:

Treatment Arm I (Bispecific Antibodies (BsAb)):

is for children, adolescents and young people with relapsed/refractory B-NHL in first relapse (only one prior line of therapy) or subsequent relapse (more than one prior line of therapy), including those achieving insufficient response (partial response (PR), Stable disease (SD), or progressive disease (PD)) to ADC therapy with standard chemotherapy to progress to transplantation or those without available CAR T-cells. 

Treatment arm II (Antibody-Drug Conjugates (ADC) with standard chemotherapy):

is for children, adolescents and young people with relapsed/refractory B-NHL in first relapse (only one prior line of therapy) or subsequent (more than one prior line of therapy) relapse, including those achieving insufficient response  to BsAb therapy to progress to transplantation or those without available CAR T-cells. 

Treatment arm III (Chimeric Antigen Receptor (CAR) T-cells):

is for children, adolescents and young people with relapsed/refractory B-NHL who have had insufficient response (PR, SD, PD) to prior therapy to progress to transplantation and have CAR T-cell product available.

If your child falls into one of the above groups, they must also meet all of the below criteria (which your child’s oncologist will determine):

• Histologically proven mature B-NHL (Diffuse Large B-Cell Lymphoma (DLBCL), Burkitt Lymphoma/Leukemia 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
• Aged from birth to 25 years old at the time of trial registration
• Medically fit to receive treatment (meets the minimum requirements for bone marrow function, liver function and kidney function listed in the trial protocol)
• Life expectancy of more than 8 weeks
• Evaluable disease as per the international paediatric NHL response criteria

Your child must also not meet any of the following criteria (which your child’s oncologist will determine):

• B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
• Patients within 90 days of an allogenic HSCT procedure
• Patients within 45 days of an autologous HSCT procedure 
• Patients within 28 days of experiencing graft versus host disease (GvHD) requiring therapy, and/or immunosuppressive treatment
• Patients within 90 days of receiving craniospinal radiation or 14 days of any other radiation
• Patients who have received any CAR T-cell therapy or other cellular therapies within a certain time window (time window dependent on treatment arm)
• Patients who are pregnant or breastfeeding
• Patients who cannot regularly be followed up due to psychological, social, geographical or other issues
• Patients for whom non-compliance with treatment or trial procedures is expected
• Uncontrolled concomitant infection
• Positive HIV serology
• Hepatitis B carrier status history of Hepatitis B Virus or positive serology
• Live vaccine within 28 days prior to trial entry 
• Known history of hypersensitivity to any of the treatments or excipients

The trial is aiming to recruit up to 30 patients in each treatment arm. Some treatment arms may fill up faster than others. Once a treatment arm is full, a new medicine of the same type will take its place.

A group called the Trial Steering Committee will review the trial data at certain points, and may decide to pause recruitment, or remove a medicine, if it does not appear to be working to help the children in the trial. If this happens, a new medicine will replace it.

As the trial goes on, the research team may identify other types of treatment that they think may work for children with relapsed/refractory B-NHL. If this happens, new treatment arms could be added to the trial.

Glo-BNHL is open to recruitment in the UK at the following centres:

• Birmingham Children's Hospital
• Bristol Royal Hospital for Children
• Royal Manchester Children's Hospital 

• Lay summary [PDF 210KB]