BridgeMD
Glo-BNHL: A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
EU CTIS ID: 2024-510575-38-00
What this study is testing
Treatment Arm I: BsAb: Estimate the clinical efficacy of BsAb treatment in patients with relapsed or refractory B-NHL in either first (only one prior line of therapy) or subsequent relapse (more than one prior line of therapy) Treatment Arm II: ADC with standard chemotherapy: Estimate the clinical efficacy of ADC treatment with modified R-ICE (rituximab, ifosfamide, carboplatin, etoposide and dexamethasone) chemotherapy in patients with relapsed or refractory B-NHL in first (only one prior line of therapy) or subsequent relapse (more than one prior line of therapy) Treatment Arm III: CAR T-cells: Estimate the efficacy of CAR T-cell therapy in relapsed or refractory BNHL patients who have CAR T-cell product available
- Phase II and Phase III (Integrated)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Histologically proven mature high-grade B-NHL classified according to either: o the 5th edition of the World Health Organisation (WHO) Classification of Haematolymphoid Tumours (WHO-HAEM5), 2022 (diffuse large B-cell lymphoma - not otherwise specified (DLBCL - NOS), high-grade B-cell lymphoma with MYC and BCL-2 rearrangements, primary mediastinal large B-cell lymphoma, Burkitt’s lymphoma, and high-grade B-cell lymphoma - NOS) at initial diagnosis; or o the revised 4th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, 2017 (diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma/leukaemia or Burkitt-like lymphoma with 11q aberration, primary mediastinal large B-cell lymphoma (PMLBL), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements and high-grade B-cell lymphoma - 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. In the following circumstances biopsy is mandated: o Relapsed or refractory disease following previous targeted therapy; biopsy required to confirm continuing target positivity (see individual treatment arms for specific relevant targets), confirmed by immunohistochemistry or flow cytometry o Relapsed disease occurring more than two years after previous therapy; biopsy required to confirm relapsed disease o Relapsed or refractory disease following previous therapy within the Glo-BNHL platform; biopsy required to confirm relapsed disease o Partial Response (PR) to previous therapy; biopsy required to confirm active residual disease
- Evaluable disease as per the Revised International Paediatric Non-Hodgkin Lymphoma Staging System (Appendix 9), including: o at least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest dimension; o or at least one bi-dimensionally measurable extra-nodal lesion >1.0 cm in its longest dimension on computerised tomography (CT) or Magnetic Resonance Imaging (MRI); o or bone marrow involvement (≥25% involvement from bone marrow, if only site of disease. Any standard method of assessment is acceptable i.e. cytomorphology, flow cytometry and/or immunohistochemistry); o or, dependent on treatment arm, evaluable Central Nervous System (CNS) only disease (evaluable by imaging or Cerebrospinal Fluid (CSF) analysis)
- Aged from birth to ≤25 years old at the time of trial entry
- Performance status ≥50 using Karnofsky or Lansky performance scores
- Life expectancy of ≥8 weeks
You likely can't join if
- B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
- 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: o Unimmunized and HBsAg and/or anti-HBs antibody and/or anti-HBc antibody positive, or o 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
See the full eligibility criteria
Who can join
- Histologically proven mature high-grade B-NHL classified according to either: o the 5th edition of the World Health Organisation (WHO) Classification of Haematolymphoid Tumours (WHO-HAEM5), 2022 (diffuse large B-cell lymphoma - not otherwise specified (DLBCL - NOS), high-grade B-cell lymphoma with MYC and BCL-2 rearrangements, primary mediastinal large B-cell lymphoma, Burkitt’s lymphoma, and high-grade B-cell lymphoma - NOS) at initial diagnosis; or o the revised 4th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, 2017 (diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma/leukaemia or Burkitt-like lymphoma with 11q aberration, primary mediastinal large B-cell lymphoma (PMLBL), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements and high-grade B-cell lymphoma - 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. In the following circumstances biopsy is mandated: o Relapsed or refractory disease following previous targeted therapy; biopsy required to confirm continuing target positivity (see individual treatment arms for specific relevant targets), confirmed by immunohistochemistry or flow cytometry o Relapsed disease occurring more than two years after previous therapy; biopsy required to confirm relapsed disease o Relapsed or refractory disease following previous therapy within the Glo-BNHL platform; biopsy required to confirm relapsed disease o Partial Response (PR) to previous therapy; biopsy required to confirm active residual disease
- Evaluable disease as per the Revised International Paediatric Non-Hodgkin Lymphoma Staging System (Appendix 9), including: o at least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest dimension; o or at least one bi-dimensionally measurable extra-nodal lesion >1.0 cm in its longest dimension on computerised tomography (CT) or Magnetic Resonance Imaging (MRI); o or bone marrow involvement (≥25% involvement from bone marrow, if only site of disease. Any standard method of assessment is acceptable i.e. cytomorphology, flow cytometry and/or immunohistochemistry); o or, dependent on treatment arm, evaluable Central Nervous System (CNS) only disease (evaluable by imaging or Cerebrospinal Fluid (CSF) analysis)
- Aged from birth to ≤25 years old at the time of trial entry
- Performance status ≥50 using Karnofsky or Lansky performance scores
- Life expectancy of ≥8 weeks
- Adequate bone marrow function documented by: o Platelet count ≥50 x 10^9/L (no platelet transfusion therapy within seven days prior to treatment) unless bone marrow involvement o Absolute neutrophil count (ANC) ≥0.75 x 10^9/L (no granulocyte colony stimulating factor within 2 days prior to treatment) unless bone marrow involvement
- Documented negative pregnancy test for female patients of childbearing potential within seven days prior to trial entry
- Patients of reproductive potential must agree to use effective contraception whilst on trial treatment and for 12 months following treatment discontinuation. - o Patients of reproductive potential using oral hormonal contraception must use an additional barrier method such as condoms whilst on trial treatment and for 12 months following treatment discontinuation (see Appendix 2 for details).
- Patients of reproductive potential must agree not to donate sperm or eggs whilst on trial treatment and for 12 months following treatment discontinuation
- Written informed consent given by patient and/or parents/legal representative
- Treatment Arm I: Patients of reproductive potential must agree not to donate sperm or eggs whilst on trial treatment and for 6 months following treatment discontinuation
- Treatment Arm I: Patients of reproductive potential using oral hormonal contraception must use an additional barrier method such as condoms whilst on trial treatment and for 12 months following treatment discontinuation
- Treatment Arm I: Adequate renal function, by measured creatinine clearance >45 ml/min (if creatinine levels are normal for the patient’s age, estimated creatinine clearance is sufficient. This must be estimated using the Cockroft-Gault Equation)
- Treatment Arm I: Adequate hepatic function documented by: o Alanine aminotransferase (ALT) ≤5 x upper limit of normal (ULN); if ALT not measured, aspartate aminotransferase (AST) ≤5 x ULN (ALT or AST <5 x ULN if attributed to lymphoma infiltration of liver) o Total bilirubin ≤1.5 x ULN Patients with known Gilbert syndrome will be excluded if the total bilirubin value is >4 x ULN for the local general population
- Treatment Arm I: Patients who have received CAR T-cell therapy or other cellular therapies more than 28 days prior must demonstrate recovery from acute toxicities and have measurable disease
- Treatment Arm II: Adequate renal function, by measured glomerular filtration rate (GFR) >60 ml/min/1.73 m^2 (estimated GFR may alternatively be used, but must be based on cystatin C)
- Treatment Arm II: Adequate hepatic function documented by: o Alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); if ALT not measured, aspartate aminotransferase (AST) ≤2.5 x ULN (ALT or AST <5 x ULN if attributed to lymphoma infiltration of liver) o Alkaline phosphatase (ALP) ≤ 2.5 x ULN (<5 x ULN if attributed to lymphoma infiltration of liver) o Total bilirubin ≤1.5 x ULN Patients with known Gilbert syndrome will be excluded if the total bilirubin value is >4 x ULN for the local general population
What rules you out
- B-cell Acute Lymphoblastic Leukaemia (B-ALL)/B-cell Lymphoblastic Lymphoma (B-LBL)
- 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: o Unimmunized and HBsAg and/or anti-HBs antibody and/or anti-HBc antibody positive, or o 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
- Treatment Arm I: Central Nervous System (CNS) only disease
- Treatment Arm I: Patients within 28 days of any CAR-T cell therapy or other cellular therapies
- Treatment Arm I: Patients within 90 days of receiving craniospinal irradiation
- Treatment Arm I: 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
- Treatment Arm I: Known CD20 negative disease at initial diagnosis
- Patients with post-transplant lymphoproliferative disorder (PTLD)
- Treatment Arm I: Seizure within the last 12 months
- Treatment Arm I: Prior treatment with CD20 x CD3 bispecific therapy
- Treatment Arm I: Known hypersensitivity to both allopurinol and rasburicase
- Treatment Arm II: Patients aged <6 months old at the time of trial entry
- Treatment Arm II: Patients within 42 days of any CAR-T cell therapy or other cellular therapies
- Treatment Arm II: 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)
- Treatment Arm II: Steroid treatment for more than a total of seven days in the 14 days prior to trial entry
- Treatment Arm II: Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- Patients with primary CNS lymphoma
- Patients within: o 90 days after an allogenic HSCT procedure o 45 days after an autologous HSCT procedure o Patients within 28 days of systemic therapy and/or immunosuppressive treatment for Graft versus Host Disease (GvHD) o 14 days of previous investigational treatment o 28 days of receiving craniospinal radiation, unless otherwise specified in the treatment arm specific eligibility criteria; or 14 days of any other radiation
- Patients who have ongoing acute toxicities from most recent lymphoma directed therapy (any toxicity ≥ grade 3 not otherwise defined in the exclusion criteria)
- Patients who have received any cytoreductive or other chemotherapy in the last 7 days prior to trial entry
- Patients with known DNA repair disorder or known primary immunodeficiency
- Patients who are pregnant or breastfeeding (exclusively or partially)
- Patients for whom non-compliance with treatment, trial procedures, or protocol follow up schedule is expected and all available resources to facilitate inclusion have been exhausted
The study team makes the final eligibility decision.
Where it's taking place
- New Zealand
- Switzerland
- Israel
- Australia
- United Kingdom
- United States
- Canada
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include New Zealand; Switzerland; Israel; Australia; United Kingdom; United States and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.