NCT06446128招募中早期 1 期
A Dose Escalating Study of CD19/CD22/BCMA Three Targets Autologous Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity(DLT)
研究概览
简要总结
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous chimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA in patients with relapsed or refractory B cell non-Hodgkin lymphoma.
详细描述
This is a single arm, open-label, dose escalation investigator initiated (IIT) study, the primary objective is to evaluate the safety and tolerability of CD19/CD22/BCMA CAR-T therapy in patients with B cell non-Hodgkin lymphoma, and determine the maximum tolerated dose (MTD). For the secondary objectives, pharmacokinetics(PK), survival of CAR-T cells in vivo, pharmacodynamics (PD) and efficacy in R/R B cell NHL will be evaluated.
This study flow comprises of a screening phase( ≤28 days prior to apheresis), apheresis phase (occur upon enrollment, ≤10 days prior to infusion), lymphodepletion phase (from Day -5 to Day -3) ,infusion of CD19/CD22/BCMA CAR-T cells on Day0, DLT assessments phase from Day1 to Day 28 and post-treatment follow-up phase (Day 29 and up to end of the study).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are diagnosed with relapsed/refractory B cell non-Hodgkin lymphoma , especially
- •Diffuse Large B Cell Lymphoma, not other specified (DLBCL,NOS),
- •Primary Mediastinal Large B Cell Lymphoma (PMBCL)
- •Transformation Follicular Lymphoma (TFL)
- •High grade B-cell lymphoma(HGBCL)
- •High grade B-cell lymphoma (HGBCL) with MYC(myelocytomatosis oncogene) and BCL2(B-cell lymphoma2) /BCL6 (B-cell lymphoma6) rearrangement
- •Refractory diseases are defined as one of the following
- •No response to last line of therapy: i. Progressive disease (PD) as best response to most recent therapy regimen; ii. Stable disease (SD) as best response to most recent therapy regimen
- •Not candidate for autologous stem cell transplant (ASCT) or refractory post-ASCT: i. Disease progression (PD) or relapsed ≤12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy
- •Individuals must have received adequate prior therapy including at a minimum:
- •anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and
- •an anthracycline containing chemotherapy regimen
- •Immunohistochemical staining shows at least two of B cell surface receptor antigen CD19,CD20, BCMA are positive(including weak, medium and strong positive)
- •At least one measurable lesion during the screening based on the recommendation for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma.
- •Life expectancy ≥ 12 weeks
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- •Adequate renal, hepatic, pulmonary and cardiac function defined as:
- •Renal function: Serum creatinine ≤ 1.5 upper limit of normal(ULN), or eGFR ≥ 60 mL/min/1.73m2 [eGFR(estimated glomerular filtration rate)=186×age^-0.203×SCr^-1.154（mg/dl）,female×0.742]
- •Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 ULN and ii: total bilirubin ≤ 2 ULN, except in individuals with Gilbert syndrome (in Gilbert's syndrome patients, those with total bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN can be enrolled).iii: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN Pulmonary: Have the minimum level of pulmonary reserve, defined as ≤ CTCAE (Common Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen saturation)≥ 91% on room air
- •Cardiac: left ventricular ejection fraction (LVEF) ≥50% determined by echocardiogram(ECG) or multigated acquisition scan (MUGA)
- •Adequate bone marrow function, define as:
- •absolute neutrophil count (ANC) ≥1 ×10^9/L
- •absolute lymphocyte count (ALC)≥ 0.5 ×10^9/L
- •Platelets ≥50 ×109/L；
- •Hemoglobulin ≥80 g/L; patients with bone marrow involvement can be enrolled if globulin>60 g/L
- •Female of child-bearing age and male participants must agree to use effective contraceptive methods until no CAR-T cells can be detected by PCR(polymerase chain reaction) test.
排除标准
- •Individuals who have antiCD45 or antiCD3 therapy
- •Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of primary or secondary CNS (central nervous system) lymphoma, cerebrospinal fluid malignant cells or brain metastases
- •Presence or history of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- •History of allogeneic stem cell transplantation
- •Any of the following situations:
- •HBsAg/ HBeAg positive; HBeAb/HBcAb positive and HBV(hepatitis B virus) DNA copies above the lower test limit;
- •HCV(hepatitis C virus) RNA positive
- •HIV(human immunodeficiency virus) positive or treponema pallidum positive
- •Presence of active or life-threatening fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
- •Individuals presence of unstable angina or myocardial infarction within 6 months of screening, or other severe/uncontrolled diseases during the screening (eg. Unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
- •Presence of uncontrolled arrhythmia with treatment
- •Pregnancy or breastfeeding women
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
CD19/CD20/BCMA CAR T therapy
Experimental
The safety and tolerability of BZE2204 will be assessed in a "1+1+1+3" and "3+3" dose escalation approach in different B-cell non-hodgkin lymphoma
干预措施: CD19/CD20/BCMA CAR T cells (Biological)
结局指标
主要结局
Dose-limiting toxicity(DLT)
时间窗: Day0-Day28
Safety
Maximum tolerated dose (MTD)
时间窗: Day0-Day28
Tolerability
次要结局
- Maximum Plasma Concentration(Cmax)(Day0-Day28，Day0-undetectable for CAR positive T cells)
- Maximum Plasma Concentration Time (Tmax)(Day0-Day28，Day0-undetectable for CAR positive T cells)
- Area Under Curve (AUC)(Day0-Day28，Day0-undetectable for CAR positive T cells)
- Cytokines ( IL(interleukin)-2, IL-4, IL-6, IL-8, IL-10, IL-15, IFN(interferon)-γ, TNF(tumor necrosis factor)-α and MCP( monocyte chemoattractant protein)-1)(Day0-Day28)
- Overall survival (OS)(Day28,Month2,Month3,Month6,Month9,Month12,Month18,Month24)
- CAR positive T cells(Day0-Day28，Day0-undetectable for CAR positive T cells)
- Progression-free survival (PFS)(Day28,Month2,Month3,Month6,Month9,Month12,Month18,Month24)
研究者
研究点 (1)
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