A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
- Conditions
- B-cell Non Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT05991388
- Lead Sponsor
- University of Birmingham
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 210
Not provided
-
B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
-
Patients within:
- 90 days after an allogenic HSCT procedure
- 45 days after an autologous HSCT procedure
- 28 days of experiencing graft versus host disease (GvHD) requiring systemic therapy, and/or immunosuppressive treatment
- 14 days of previous investigational treatment
- 28 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
-
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:
- Unimmunized and HBsAg and/or anti-HBs antibody and/or anti- HBc antibody positive,
- Immunized and HBsAg and/or anti-HBc antibody positive.
-
Live vaccine within 28 days prior to trial entry
-
Known history of hypersensitivity to any of the treatments or excipients
Exclusion criteria applicable to treatment arm I only:
- Central Nervous System (CNS) only disease
- Patients within 28 days of any CAR-T cell therapy or other cellular therapies
- 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
- Known CD20 negative disease at initial diagnosis
- Seizure within the last 12 months
- Prior treatment with CD20 x CD3 bispecific therapy
- Known hypersensitivity to both allopurinol and rasburicase
Exclusion criteria applicable to treatment arm II only:
- Patients within 42 days of any CAR-T cell therapy or other cellular therapies
- 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)
- Steroid treatment for more than a total of seven days in the 14 days prior to trial entry
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE Carboplatin Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles) Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE Ifosfamide Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles) Treatment Arm I - BsAb - Odronextamab Odronextamab 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 Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE Rituximab Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles) Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE Etoposide Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles) Treatment Arm III - CAR T-cells - TBC CAR T-cells (TBC) Patients will receive CAR-T cell therapy - agent TBC Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE Etoposide Phosphate Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles) Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE Loncastuximab tesirine Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles) Treatment Arm II - ADC with Standard Chemotherapy - Loncastuximab tesirine with modified R-ICE Dexamethasone Patients will receive loncastuximab tesirine given as a 30-minute intravenous infusion with each cycle of modified R-ICE (maximum three cycles)
- Primary Outcome Measures
Name Time Method Treatment Arm II: ADC with standard chemotherapy: Occurrence of CR At the end of Cycle 2 and Cycle 3 of treatment (each cycle is 28 days) 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)
Treatment Arm I: BsAb: Occurrence of an objective response (OR) At the end of week 12 of treatment 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)
- Secondary Outcome Measures
Name Time Method Occurrence of an objective response (OR), where relevant At the end of cycles 1, 2, and 3 (each cycle is 28 days) Treatment arm specific
Overall survival time (OS) From start of treatment until last patient has been followed up for 2 years All treatment arms
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) All treatment arms
Duration of response (DOR) From start of treatment until last patient has been followed up for 2 years All treatment arms
Occurrence of treatment emergent adverse events (TEAEs), where relevant From start of treatment until 90 days after last dose Treatment arm specific
Event-free survival time (EFS) From start of treatment until last patient has been followed up for 2 years All treatment arms
Occurrence of adverse events of special interest (AESI) From start of treatment until 90 days after last day of treatment Treatment arm specific
Progression-free survival time (PFS) From start of treatment until last patient has been followed up for 2 years All treatment arms
Trial Locations
- Locations (3)
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom