NCT05535673尚未招募1 期
A Single Dose-escalation Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Allogeneic CAR-T Targeting CD19 in Patients With Refractory or Relapsed B Cell Lymphoma
Zhengzhou University0 个研究点目标入组 15 人开始时间: 2022年9月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15
- 主要终点
- Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage
研究概览
简要总结
This is a single dose escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A (Allogeneic CAR-T targeting CD19) in patients with refractory or relapsed CD19 positive B cell Lymphoma.
详细描述
This is a single-center, nonrandomized, open-label, dose-escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A in patients with refractory or relapsed CD19 positive B cell Lymphoma, such as Diffuse large B-cell lymphoma (DLBCL) , follicular lymphoma and etc.
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
- •Male or female aged ≥ 18 years old;
- •Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2017, including follicular lymphoma (FL), marginal zone lymphoma (MZL, including SMZL, NMZL and extranodal MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), etc;
- •Relapsed or refractory B-cell NHL.
- •Adequate treatment :
- •Follicular lymphoma should be treated with at least two prior treatment including alkylating agents and anti-CD20 mAbs;
- •Marginal zone lymphoma should be treated with at least two prior treatment including anti-CD20 mAbs;
- •mantle cell lymphoma should be treated with a first-line therapy including anthracyclines/bendamoxetine+anti-CD20 mAbs;
- •Diffuse large B lymphoma, not otherwise specified (DLBCL, NOS), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit lymphoma, DHL/THL), diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL), histological grade 3b follicular lymphoma. relapsed or primary refractory lymphoma within 12 months after first-line treatment, first-line therapy including anthracycline and anti-CD20 mAbs.
- •Failing to autologous CAR-T therapy.
- •Estimated life expectancy > 12 weeks deemed by investigator；
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •At least one measurable lesion, with any nodal lesion > 15mm in the longest diameter and any extranodal lesion > 10mm in the longest diameter.
- •Adequate bone marrow, renal, hepatic, pulmonary and cardiac function;
- •Should be confirmed Cluster of differentiation(CD)19 positive by biopsy for the patient who received target CD19 therapy before.
排除标准
- •Allergic to preconditioning measures.
- •HP-positive MALT;
- •Patients with risks of deep gastrointestinal ulcers, perforation or gastrointestinal bleeding
- •Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.
- •Uncontrollable bacterial, fungal and viral infection during screening.
- •Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment.
- •Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment.
- •Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening.
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment.
- •Had big lesion(single lesion diameter ≥7.5 cm).
- •Receive allogeneic hematopoietic stem cell transplantation less than 100 days.
- •Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) .
- •Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.
- •Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.
研究组 & 干预措施
ThisCART19A cell injection
Experimental
In this study, allogeneic anti-CD19 CART cell (This CART19A) injection is used to treat patients with refractory or relapsed CD19 positive B cell Lymphoma.
干预措施: ThisCART19A (Drug)
结局指标
主要结局
Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage
时间窗: 28 days
DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.
The incidence of all grade TEAEs and ≥3 grade TEAEs during dose escalation stage
时间窗: Up to 2 years after ThisCART19A infusion
Incidence of treatment-emergent adverse events (TEAEs) and ≥3 grade TEAEs
Objective Response Rate in patient with NHL during dose expansion stage
时间窗: 12 months
the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment
次要结局
- Analysis the severity and Incidence of Adverse Events in each dose level during dose escalation and dose expansion stage(3 months)
- Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages(6 months)
- the change characteristics of immune effect cells number during dose escalation and expansion stages(3 months)
- Analysis the change characteristics of cytokines during dose escalation and expansion stages (IL-1β/IL-2/IL-4/IL-5/IL-6/IL-8/IL-10/IL-12p70/IL-17A/IL-17F/IL-22/TNF-α/TNF-β)(3 months)
- Duration of response (DOR) during dose escalation stage and expansion stage(12 months)
- Progress-free survival (PFS) during dose escalation stage and expansion stage(12 months)
- OS(overall survival) during dose escalation stage and expansion stage(12 months)
研究者
Mingzhi Zhang
Principal Investigator
Zhengzhou University
相似试验
Unknown
1 期
Study of Safety and Biomarker Efficacy of TS23 in Healthy VolunteerThrombosisCerebral IschemiaMyocardial InfarctionVenous ThrombosisPulmonary EmbolismNCT03001544Translational Sciences, Inc.24
已完成
1 期
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Subcutaneous Infusions of ABBV-951 in Subjects With Parkinson's DiseaseParkinson's Disease (PD)NCT03033498AbbVie29
已完成
1 期
A Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Orally Administered DAA-I in Healthy SubjectsHealthyNCT02666196National University Hospital, Singapore18
已完成
1 期
A Safety and Pharmacokinetics Study of ZB004 in Healthy ParticipantsHealthy VolunteersNCT05794516Zenas BioPharma (USA), LLC40
已完成
1 期
MK-1006 Single Dose Study in Japanese Type 2 Diabetes Patients (MK-1006-005)Diabetes Mellitus, Non-Insulin-DependentNCT00791661Merck Sharp & Dohme LLC24