A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
- 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 Bur...
- 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...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 210
Not provided
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B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
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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
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Patients with known DNA repair disorder or known primary immunodeficiency
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Patients who are pregnant or breastfeeding (exclusively or partially)
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Patients who cannot regularly be followed up in accordance with the protocol due to psychological, social, geographical or other issues
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Patients for whom non-compliance with treatment or trial procedures is expected
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Uncontrolled concomitant infection. Severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of trial entry
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Known HIV positivity
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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