NCT06689917招募中不适用
An Early Exploratory Clinical Study of the Safety, Tolerability and Preliminary Efficacy of JY231 Injection in the Treatment of Relapsed or Refractory B-cell Lymphoma/Leukaemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of adverse events(AE) after infusion
研究概览
简要总结
This study is an investigator-initiated single center, single arm clinical study with a target population of patients with relapsed or refractory B cell lymphoma / leukemia. It is an early exploratory clinical study of the safety, tolerability and initial efficacy of JY231 injection in the treatment of relapsed or refractory B cell lymphoma / leukemia.
详细描述
This open-label, single-arm study is designed to evaluate the efficacy and safety of in vivo CAR-T cell therapy in patients with relapsed/refractory B-cell lymphoma/leukaemia. This study incorporates two pretreatment regimens: lymphodepletion and non-lymphodepletion.
In the lymphodepletion regimen:
Upon enrolment, leukapheresis will be performed. Subjects will then undergo 3-5 days of lymphodepleting therapy with fludarabine and cyclophosphamide, followed by concomitant intravenous infusion of the JY231 preparation and autologous peripheral blood mononuclear cell(PBMC) via a double-lumen catheter.
In the non-lymphodepletion regimen:
Patients will receive direct intravenous injection of the JY231 preparation.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject voluntarily sign informed consent and are willing and able to comply with all trial requirements;
- •Age is 18-75 years old and gender is not limited;
- •Malignancy cells in bone marrow or peripheral blood are Cluster of Differentiation 19 - positive(CD19+) detected by flow cytometric analysis;
- •Meet the clinical criteria for relapsed or refractory B-cell lymphoma, including: indolent lymphoma (iNHL), such as follicular lymphoma (FL) and marginal zone lymphoma (MZL); aggressive B-cell lymphoma, like diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL), and T-rich lymphocyte-bearing large B-cell lymphoma (TCRBCL), or have a diagnosis of acute B-lymphocytic leukemia (B-ALL) and meet one of the following conditions:
- •Refractory B-ALL: those who did not achieve complete remission after 2 courses of standard induction regimen chemotherapy, or those who did not achieve complete remission after first-line or multi-line salvage chemotherapy;
- •Relapsed B-ALL: relapse within 12 months after first remission, or relapse after first-line / multi-line salvage chemotherapy;
- •Relapse after autologous or allogeneic hematopoietic stem cell transplantation; In addition, patients with Philadelphia chromosome positive (Ph +) should be relapsed after at least two tyrosine kinase inhibitors (TKI) treatment, or they could not tolerate TKI therapy, or have a t315i mutation, resistant to TKI drugs.
- •Morphological examination of bone marrow cells showed the proportion of primitive and naive lymphocytes was> 5%;
- •No Hematopoietic Stem Cell Transplantation(HSCT) within 6 months before enrollment;
- •At least one measurable lesion was imaging for relapsed or refractory B cell lymphoma, long diameter of> 15mm, or extranodal lesion of> 10mm, along with a positive Positron Emission Tomography - Computed Tomography(PET-CT) examination.
- •More than 12 weeks of expected survival period
- •Baseline Eastern Cooperative Oncology Group(ECOG) score was 0-1;
- •Adequate organ function (criteria regarding liver and kidney function can be moderately relaxed):
- •Glutamic aminotransferase (ALT) ≤3 times upper limit of normal (ULN);
- •Grass aminotransferase (AST) ≤3 times ULN;
- •Total bilirubin ≤1.5 times ULN;
- •Serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 60 mL/min;
- •Indoor oxygen saturation ≥ 92%;
- •Left ventricular ejection fraction (LVEF)≥55%, echocardiography confirmed no pericardial effusion and no clinically significant ECG findings;
- •There is no clinically significant pleural effusion;
- •Adequate bone marrow reserve without transfusion, defined as:
- •Absolute neutrophil count (ANC)>1.000 / mm3;
- •Absolute lymphocyte count (ALC)≥ 300 / mm3;
- •Platelet≥50.000/mm3;
- •Hemoglobin>8.0 g/dl;
- •Subjects using the following drugs need to meet the following conditions:
- •Steroids: The therapeutic dose of steroids must be stopped 72 hours before JY231 infusion. However, physiological alternative doses of steroids are allowed;
- •Immunosuppression: Any immunosuppressive drug must be stopped at ≥4 weeks prior to enrollment;
- •Antiproliferative therapy other than lymphodepletion chemotherapy within two weeks of infusion;
- •Cluster of Differentiation 20(CD20) antibody-related therapy must be stopped within 4 weeks before infusion or 5 half-lives after the CD20 antibody;
- •CNS disease prophylaxis must be stopped 1 week before JY231 infusion (e. g. intrathecal methotrexate).
- •Reproductive men, sexual partners ensure effective contraception; fertile women, adopted effective contraception and agreed to use contraception throughout the study period.
排除标准
- •Subjects with active cerebrospinal fluid malignant cells or brain metastases, or subjects with active central nervous system (CNS) lymphoma, or CNS leukaemia;
- •Subjects with a history of active CNS disease, such as seizures, cerebrovascular ischemia / hemorrhage, dementia, cerebellar disease, or any autoimmune disease associated with CNS involvement;
- •Subjects who have received other study drugs within 30 days before screening, or are still in the washout period;
- •Patients who have previously received any anti-CD19 / anti-Cluster of Differentiation 3(CD3) therapy or any other anti-CD19 therapy (except for those with normal T cell numbers and function and with CD19-positive tumors);
- •Patients who have been previously treated with any gene therapy product, including Chimeric Antigen Receptor T(CAR-T) therapy (except patients who do not have CAR-T cells in vivo and have normal T cell number and function and are with CD19 positive tumors);
- •Subjects with radiation therapy within 2 weeks prior to the infusion;
- •Subjects with active hepatitis B (defined as Hepatitis B Virus(HBV) DNA test value> 500 IU / mL) or hepatitis C (HCV RNA positive); subjects with HIV positive or treponema pallidum positive;
- •Subjects with uncontrolled acute life-threatening bacterial, viral, or fungal infection (e. g. positive blood culture 72 hours before infusion);
- •Subjects with unstable angina pectoris and / or myocardial infarction within the 6 months prior to screening;
- •Subjects with concurrent or previously diagnosed with other malignancies, except for the patients under following conditions:
- •Well treated basal cells, papillary thyroid carcinoma, squamous cell carcinoma (adequate wound healing is required before enrollment into this study);
- •Carcinoma in situ of cervical cancer or breast cancer, after curative treatment, showed no signs of recurrence for at least 3 years before the study;
- •The primary malignancy has been completely removed and is in complete remission for 5 years.
- •Arrhythmic subjects without medical management control;
- •Subjects receiving oral anticoagulation within 1 week before JY231 injection infusion;
- •Having active neurological autoimmune or inflammatory conditions (such as Guillain-Barre syndrome, amyotrophic lateral sclerosis);
- •Female subjects in pregnant or lactating, or women with planned pregnancy within 2 years after JY231 infusion or male partner with planned pregnancy within 2 years after JY231 infusion;
- •Subjects with taboo study procedures or other medical conditions that may put them at unacceptable risk according to the investigator's judgment and / or clinical criteria.
- •Other conditions that the investigator believes that the subjects should not be enrolled in this clinical trial, such as poor compliance.
研究组 & 干预措施
JY231 injection for the treatment of relapsed or refractory B cell lympho Early exploratory clinica
Experimental
JY231 Injection for the Treatment of relapsed or refractory B cell lymphoma/ leukemia subjects who meet the inclusion criteria will receive intravenous JY231. JY231 infusion will produce CAR-T cells in the body.
干预措施: JY231 Injection (Drug)
结局指标
主要结局
Incidence of adverse events(AE) after infusion
时间窗: Day 28、Month 2、Month 3、Month 6、Month 12、Month 18、Month 24
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included.
Maximal Tolerated Dose(MTD)
时间窗: Up to 28 days after infusion
MTD will be determined based on Dose-Limiting Toxicity(DLTs) observed during the first 28 days of study treatment.
次要结局
- Objective Response Rate(Day 28、Month 2、Month 3、Month 6、Month 12、Month 18、Month 24)
研究者
研究点 (1)
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