临床试验/NCT05350787

NCT05350787

已完成

1 期

To Evaluate the Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Relapsed and Refractory Acute B-cell Leukemia

Zhejiang University2 个研究点分布在 1 个国家目标入组 10 人2022年3月18日

适应症B-ALL

干预措施ThisCART19A

概览

阶段: 1 期
干预措施: ThisCART19A
疾病 / 适应症: B-ALL
发起方: Zhejiang University
入组人数: 10
试验地点: 2
主要终点: Dose limited toxicity(DLT) observation and the incidence of treatment-emergent adverse events(TEAE) which more than or equal to grade 3 in each dose level
状态: 已完成
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is an open label, phase I study to assess the safety, efficacy and pharmacokinetics of ThisCART19A in patients with relapsed and refractory acute B-cell leukemia

注册库

clinicaltrials.gov

开始日期

2022年3月18日

结束日期

2025年5月21日

最后更新

2个月前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Zhejiang University

责任方

Principal Investigator

主要研究者

He Huang

President/Proffessor

Zhejiang University

入排标准

入选标准

•All subjects or legal representatives must sign a voluntary letter of consent approved by the IRB in person prior to the commencement of any screening procedure;
•Patients diagnosed with B-ALL according to the Chinese Guidelines for the Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2021 edition);
•There is no gender limitation, age 18-70(upper limit not included);
•Consistent with the diagnosis of recurrent refractory B-ALL. Recurrence： was defined as the recurrence of lymphoblasts（≥5%） in peripheral blood or bone marrow or extramedullary diseasefor patients who had acquired CR ; Refractory ：was defined as failure to CR or CRi at the end of induction therapy (generally referred to 4-week regimen or Hyper-CVAD regimen);Patients with Ph+ R/R ALL who failed after 2-line TKI treatment, were intolerant to TKI treatment or were not suitable for TKI treatment;
•The following factors can coexist:
•A) Failure to prepare autologous CAR-T (definition: too few autologous lymphocytes \[200/ML\] or cannot meet the release standard); B) Experienced treatment with auto car-T/berintoomumab/ CD22 antibody conjugation drugs; C) ≥100 days after hematopoietic stem cell transplantation; D) high-risk patients (High risk was defined as a high white blood cell count ≥30×109/L at diagnosis or with poor cytogenetic prognosis);
•Hypodiploid (\<44 chromosomes);
•KMT2A rearrangement: t (4;11) or otherwise;
•t (v;q32)/IgH;
•t (9;22) (q34;q11.2) or BCR-ABL1;

排除标准

•Allergic to preconditioning measures.
•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 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 HBV or HCV or HIV or Syphilis infection. HBV-DNA \< 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenufovir, etc, and supervisory the relative indication during the treatment.
•Combined systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. Or systemic diseases that require long-term use of immunization Inhibitor.
•Vaccinated with influenza vaccine within 2 weeks prior to cleansing (SARS-COV19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) .
•Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.

研究组 & 干预措施

ThisCART19A 3×10^6 cells/kg for dose level 1

Patients will receive 3×10\^6 cells/kg of ThisCART19A

干预措施: ThisCART19A

ThisCART19A 5×10^6 cells/kg as dose level 2

Patients will receive 5×10\^6 cells/kg of ThisCART19A

干预措施: ThisCART19A

结局指标

主要结局

Dose limited toxicity(DLT) observation and the incidence of treatment-emergent adverse events(TEAE) which more than or equal to grade 3 in each dose level

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

时间窗: Up to 2 years after ThisCART19A infusion

Incidence of treatment-emergent adverse events (TEAEs) and ≥3 grade TEAEs

次要结局

Changes in cytokine level after ThisCART19A infusion.(3 months)
Changes in immune effect cells count after ThisCART19A infusion.(3 months)
The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion(3 months)
Objective response rate(At Month 1, 2, 3)
MRD response rate(24 months)