NCT05747157招募中早期 1 期
Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10- 19) in the Treatment of r/r B-ALL Clinical Research
Anhui Provincial Hospital1 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2023年2月15日最近更新:
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
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
A Study of Metabolically Armed CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia
详细描述
This is a single arm , open-label study. This study is indicated for relapsed and/or refractory CD19+ B-cell Acute Lymphoblastic Leukemia . The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products.
- Main research objectives:
To evaluate the safety and efficacy of metabolically armed CD19 CAR-T Cells in the treatment of r/r B-ALL. 2. Secondary research objectives:
A. To evaluate the pharmacokinetic (PK) and pharmacodynamics(PD) characteristics of metabolically armed CD19 CAR-T Cells after infusion.
B. To evaluate tumor remission after infusion of metabolically armed CD19 CAR-T Cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient or his/her guardian voluntarily signed the informed consent；
- •Patients with relapsed and refractory B-cell Acute Lymphoblastic Leukemia.
- •Definition of relapsed or refractory B-ALL (meeting one of the following conditions):
- •2 or more relapses;
- •Bone marrow relapsed after allo-HSCT and prepared to infuse Meta10-19 more than 6 months after allo-HSCT ;
- •CR not achieved after standardized chemotherapy;
- •Philadelphia-chromosome-positive (Ph+) patients who are ineffective or intolerant to first- and second-generation tyrosine kinase inhibitor (TKI) treatments, or who have contraindications to tyrosine kinase inhibitors;
- •The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is ≥ 5%
- •CD19 expression was positive by biopsy or flow cytometry (accept the results of this peripheral blood mononuclear cells collection or previous Class A tertiary hospital before this peripheral blood collection);
- •Expected survival time greater than 12 weeks
- •The baseline ECOG score was 0 or 1；
- •Organ function：
- •Kidney function:
- •Serum creatinine ≤1.5 times ULN, or； The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/min/1.73m2；[eGFR=186×（age）-0.203×SCr-1.154（mg/dl），for females, the result was ×0.742]；
- •Liver function： ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with Gilbert-Meulengracht syndrome. Patients with Gilbert-.Meulengracht syndrome with total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included.
- •Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment.
- •Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45％;
- •Patients using the following drugs must meet the following conditions:
- •Steroid: Therapeutic doses of steroids must be discontinued 2 weeks prior to Meta10-19 infusion. However, physiological replacement doses of steroids are permitted, hydrocortisone or its equivalent < 6-12mg/mm2/ day；
- •Immunosuppressive agent: Any immunosuppressive drug must be stopped ≥4 weeks before the informed consent is signed;
- •Anti-proliferative therapy other than preconditioning chemotherapy is discontinued within 2 weeks prior to Meta10-19 infusion；
- •Treatment for CNS disease must be stopped 1 week before Meta10-19 infusion (e.g., intrathecal methotrexate)
- •The patient has recovered from the toxicity of the previous treatment, that is, the CTCAE toxicity grade is less than 1 (The exception is specific toxicity of grade 2 or less, such as hair loss, which the researchers have determined is not recoverable in a short period of time) is suitable for pretreatment chemotherapy and CAR-T cell therapy;
- •Women of childbearing age and all male patients must consent to use an effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR-T cells in vivo.
排除标准
- •Patients with isolated extramedullary relapse;
- •Patients with confirmed diagnosis of Burkitt's lymphoma/ leukemia;
- •Patients who had received prophylaxis for CNS leukemia within 1 week prior to Meta10-19 infusion;
- •Patients with present or history of central nervous system diseases such as seizures disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
- •Patients with history of allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 6 months prior to Meta10-19 infusion;
- •Patients who had received chemotherapy other than preconditioning chemotherapy within 2 weeks prior to Meta10-19 infusion ;
- •Patients who participated in other clinical trials within 30 days prior to enrollment;
- •Patients with active hepatitis B (defined as hepatitis B surface antigen positive or hepatitis B core antibody positive, concomitant hepatitis B virus DNA level > 1000 copies/ml) or hepatitis C (HCV RNA positive);
- •Patients with HIV antibody positive or treponema pallidum antibody positive;
- •Patients with uncontrolled acute life-threatening bacterial, viral or fungal infections (e.g. positive blood cultures ≤72 hours before Meta10-19 infusion)
- •Patients with unstable angina pectoris and/or myocardial infarction within 6 months prior to enrollment；
- •Patients with history of other malignancies, but the following conditions can be enrollment:
- •Adequately treated basal or squamous cell carcinoma (requiring adequate wound healing before signing informed consent);
- •Carcinoma in situ (DCIS) of cervical or breast cancer, which has been treated therapeutically, has shown no signs of recurrence for at least 3 years prior to the signing of the informed consent；
- •The primary malignancy has been completely resected and in complete remission for ≥5 years。
- •Women who are pregnant or breastfeeding (pregnancy tests for women of childbearing age are positive);
- •Patients with active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome, amyotrophic lateral sclerosis);
- •Other conditions that the investigator considered should not be enrolled in this clinical study, such as poor compliance.
研究组 & 干预措施
Administration of Metabolically Armed CD19 CAR-T cells
Experimental
Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CAR-T cells infusion. A dose of metabolically armed CD19 CAR-T cells will be infused on day 0.
干预措施: Metabolically Armed CD19 CAR-T cells (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Within 3 months following infusion of Meta10- 19
Measure Tumor response rate (including CR and PR)
MTD
时间窗: MTD will be determined based on DLTs observed during the first 28 days of study treatment
Determine the Maximal Tolerable Dose(MTD)
次要结局
- Pharmacodynamics(Up to 28 days after infusion)
- Pharmacokinetics(Up to 12 months after CAR-T treatment)
研究者
研究点 (1)
Loading locations...
相似试验
招募中
早期 1 期
Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical ResearchDiffuse Large B-cell LymphomaNCT05715606Anhui Provincial Hospital18
招募中
早期 1 期
Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Relapsed and/or Refractory CD19-positive B Cell Hematological Malignancies Clinical ResearchNon-hodgkin LymphomaAcute Lymphoblastic LeukemiaNCT06393335The Children's Hospital of Zhejiang University School of Medicine36
招募中
早期 1 期
Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Relapsed and/or Refractory CD19-positive B Cell Hematological Malignancies Clinical ResearchNon-hodgkin LymphomaAcute Lymphoblastic LeukemiaNCT06277011Anhui Provincial Hospital18
招募中
早期 1 期
Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical ResearchDiffuse Large B-cell LymphomaNCT06120166He Huang18
招募中
1 期
Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r B-NHL Clinical ResearchNon-hodgkin Lymphoma,B CellNCT06716164Zhejiang University36