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 人开始时间: 2022年3月18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
- 已完成
- 发起方
- 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
研究概览
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
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;
- •Complex karyotype (≥5 chromosomal abnormalities);
- •BCR-ABL1-like (Ph-like) ALL;
- •JAK-STAT (CRLF2r, EPORr, JAK1/2/3r, TYK2r, mutations of SH2B3, IL7r, Jak1/2/3 );
- •ABL class( rearrangement of ABL1, ABL2, PDGFRA, PDGFRB, FGFR);
- •Other (NTRKr, FLT3r, LYNr, PTK2Br);
- •Intrachromosomal amplification of chromosome 21 (IAMP21-ALL);
- •t (17;19) : TCF3-HLF fusion ;
- •Alterations of IKZF1; E) Extramedullary lesions.
- •The expected survival time is ≥12 weeks;
- •ECOG score 0-1;
- •Had good organic function during screening
- •CD19 was still expressed in leukemia cells in bone marrow, peripheral blood or biopsy tissue by flow cytometry within one month prior to informed consent (after the last treatment).
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.
- •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.
- •Any ineligibility conditions considered by the investigator that may increase the risk of the subject or interfere with the results of the study;
研究组 & 干预措施
ThisCART19A 3×10^6 cells/kg for dose level 1
Experimental
Patients will receive 3×10^6 cells/kg of ThisCART19A
干预措施: ThisCART19A (Biological)
ThisCART19A 5×10^6 cells/kg as dose level 2
Experimental
Patients will receive 5×10^6 cells/kg of ThisCART19A
干预措施: ThisCART19A (Biological)
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)
研究者
He Huang
President/Proffessor
Zhejiang University
研究点 (2)
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