NCT05991388 A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
| NCT ID | NCT05991388 |
| Status | Recruiting |
| Phase | Phase 2, Phase 3 |
| Sponsor | University of Birmingham |
| Condition | B-cell Non Hodgkin Lymphoma |
| Study Type | INTERVENTIONAL |
| Enrollment | 210 participants |
| Start Date | 2024-05-02 |
| Primary Completion | 2031-05-01 |
Eligibility & Interventions
Eligibility Fast-Check
Enter your details for a quick preliminary check. This does not replace medical advice.
What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.
This trial targets 210 participants in total. It began in 2024-05-02 with a primary completion date of 2031-05-01.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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.
Eligibility Criteria
Inclusion criteria applicable to all treatment arms: * Histologically proven mature B-NHL (Diffuse Large B-Cell Lymphoma (DLBCL), Burkitt Lymphoma/Leukaemia 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. (Note: relapses following prior targeted therapy must have continuing target positivity, confirmed by an established method). * If relapse occurs more than two years after previous therapy, a biopsy must be performed * Evaluable disease as per the international paediatric non-Hodgkin Lymphoma response criteria, including: * at least one bi-dimensionally measurable nodal lesion \>1.5 cm in its longest dimension; * 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); * 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); * or, dependent on treatment arm, evaluable Central Nervous System (CNS) only disease (evaluable by imaging or Cerebrospinal Fluid (CSF) analysis)(\*\*) * Age 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: * Platelet count ≥50x 10\^9/L (no platelet transfusion therapy within seven days prior to treatment) unless bone marrow involvement(\*\*\*) * 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(\*\*\*) * Adequate hepatic function documented by: * Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤5 x upper limit of normal (ULN) * 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 * Documented negative pregnancy test for female patients of childbearing potential within seven days prior to trial entry * Patients of reproductive potential agrees to use effective contraception whilst on trial treatment and for 12 months following treatment discontinuation * Written informed consent given by patient and/or parents/legal representative Inclusion criteria applicable to treatment arm I only: * Male patients of reproductive potential must agree not to donate sperm whilst on trial treatment and for 6 months following treatment discontinuation * Adequate renal function, creatinine clearance \>45 ml/min by measurement or estimation (if creatinine levels are normal for the patient's age, using the Cockroft-Gault Equation is sufficient) * For patients with bone marrow involvement(\*\*\*) or splenic sequestration, adequate bone marrow function documented by: * Platelet count ≥25 x 10\^9/L (no platelet transfusion therapy within three days prior to treatment) * Haemoglobin level ≥7 g/dL * Absolute neutrophil count (ANC) ≥0.5 x 10\^9/L (no granulocyte colony stimulating factor within two days prior to treatment) * 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 Inclusion criteria applicable to treatment arm II only: * Adequate renal function, by measured glomerular filtration rate (GFR) \>60 ml/min/1.73m\^2 (estimated GFR is not sufficient) * For patients with bone marrow involvement(\*\*\*) or splenic sequestration, requirements for bone marrow function do not apply (\*) Refractory disease The following patients are considered to have refractory disease and can be included in this trial: * Patients with who do not achieve PR or CR with last therapy * Patients with partial response to last therapy (biopsy proven), with no evidence of progression (\*\*) CNS only disease Patients with CNS only disease may be eligible depending on the treatment arm. Please refer to the relevant treatment arm specific eligibility criteria. (\*\*\*) Bone marrow involvement Patients who have ≥ 25% blasts in the bone marrow are considered to have bone marrow involvement. For these patients, requirements for bone marrow function are dependent on treatment arm. Please refer to the relevant treatment arm specific eligibility criteria. Exclusion Criteria: * 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
Contact & Investigator
Amos Burke
PRINCIPAL INVESTIGATOR
University of Birmingham
Frequently Asked Questions
Who can join the NCT05991388 clinical trial?
This trial is open to participants of all sexes, up to 25 Years, studying B-cell Non Hodgkin Lymphoma. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05991388 trial and what does that mean for participants?
Phase 2 trials evaluate whether the treatment shows signs of effectiveness while continuing to monitor safety. More participants are enrolled than in Phase 1 to help refine the treatment protocol.
Is NCT05991388 currently recruiting?
Yes, NCT05991388 is actively recruiting participants. Contact the research team at glo-BNHL@trials.bham.ac.uk for enrollment information.
Where is the NCT05991388 trial being conducted?
This trial is being conducted at Sydney, Australia, Brisbane, Australia, Perth, Australia, Vienna, Austria and 7 additional locations.
Who is sponsoring the NCT05991388 clinical trial?
NCT05991388 is sponsored by University of Birmingham. The principal investigator is Amos Burke at University of Birmingham. The trial plans to enroll 210 participants.