2024-510575-38-00招募中3 期
Glo-BNHL: A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- Treatment Arm II: ADC with standard chemotherapy: 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)
研究概览
简要总结
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
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Treatment Arm II: ADC with standard chemotherapy: 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 II: ADC with standard chemotherapy: 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) 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)
Treatment Arm I: BsAb: 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)
次要结局
- Progression-free survival time (PFS)
- Overall survival time (OS)
- Best overall response (BOR) during treatment
- Event-free survival time (EFS)
- Duration of response (DOR)
- Occurrence of an objective response (OR), where relevant
- Occurrence of adverse events of special interest (AESI)
- Occurrence of treatment emergent adverse events (TEAEs), where relevant
- Pharmacokinetic profile of novel agent, where relevant
- Pharmacodynamic markers, where relevant
研究者
Clinical Trial Coordinator
Scientific
The University Of Birmingham
研究点 (4)
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