NCT04230473已完成1 期
A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)
研究概览
简要总结
This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of CNCT19 in adult patients with relapsed or refractory acute lymphoblastic leukemia.
详细描述
This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of CNCT19 in adult patients with relapsed or refractory acute lymphoblastic leukemia. The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and Follow-up, and Survival Follow-up. The total duration of the study is 2 years from CNCT19 cell infusion.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent is signed by the subject.
- •Relapsed or refractory ALL
- •Relapse within 12 months of first remission;
- •Without remission after more than 6 weeks of induction chemotherapy or without remission after 2 cycles of induction chemotherapy regimen;
- •2nd or greater Bone Marrow (BM) relapse OR;
- •First relapse after chemotherapy, without remission after at least 1 rescue treatment;
- •Any BM relapse after autologous stem cell transplantation (SCT).
- •Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months of study entry.
- •Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 1 generation and/or 2 generation of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a T315I mutation.
- •Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
- •Eastern cooperative oncology group (ECOG) performance status of 0 to
- •Adequate organ function defined as:
- •aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN);
- •Serum alanine aminotransferase (ALT) ≤ 3 upper limit of normal (ULN);
- •Total bilirubin ≤ 2 ULN, except in individuals with Gilbert's syndrome; Note: Patients with Gilbert's syndrome that bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN will be eligible;
- •A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min (Cockcroft and Gault);
- •Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen saturation > 91% on room air;
- •International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (APTT) ≤ 1.5 ULN.
- •Have appropriate vascular conditions for apheresis.
- •Non-hematological toxic reactions (excluding diseases related) caused by previous treatment were restored to ≤ 1 level before screening (excluding ≤ 2 level of neurotoxicity caused by hair loss and chemotherapy drugs).
- •Women of childbearing age have a negative blood / urine pregnancy test within 7 days before the CNCT19 infusion. Women of child-bearing potential and all male participants must use highly effective methods of contraception throughout the study and for a period of at least six months after the CNCT19 infusion.
排除标准
- •Active CNS involvement by malignancy.
- •Isolated extra-medullary disease relapse.
- •Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The following situations are excluded:
- •Lymphodepleting Chemotherapy prescribed by the protocol;
- •Tyrosine kinase inhibitors (TKI) and hydroxyurea must be stopped > 72 hours prior to CNCT19 infusion;
- •The following drugs must be stopped > 1 week prior to CNCT19 infusion: 6-mercaptopurine, 6-thioguanine, methotrexate (<25 mg / m2), cytosine arabinoside (<100 mg / m2 / d), vincristine, asparaginase;
- •Pegylated-asparaginase must be stopped > 4 weeks prior to CNCT19 infusion;
- •CNS prophylaxis treatment must be stopped > 1 week prior to CNCT19 infusion.
- •Radiotherapy before CNCT19 infusion:
- •Non-CNS site of radiation completed < 2 weeks prior to CNCT19 infusion; CNS directed radiation completed < 8 weeks prior to CNCT19 infusion.
- •Therapeutic systemic doses of steroids were stopped < 72 hours prior to CNCT19 infusion. However, the following physiological replacement doses of steroids are allowed: < 10 mg/day hydrocortisone or equivalent.
- •Has had treatment with any prior CAR-T therapy.
- •Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- •Patients with systemic vasculitis (such as Wegener granulomatosis, nodular polyarteritis, systemic lupus erythematosus) and active or uncontrolled autoimmune disease (such as autoimmune hemolytic anemia, etc.).
- •Patients who are positive for any of HBsAg, HBeAg, HBeAb, HBcAb, HCV-Ab, TP-Ab.
- •Active malignancy. Patients with Prior malignancy that has been cured for ≥ 2 years are excluded.
- •a. Left Ventricular Ejection Fraction (LVEF) ≤45%; b. III/IV congestive heart failure (NYHA); c. Severe arrhythmia ; QTc≥450ms (male)or QTc≥470ms (female)(QTcB=QT/RR1/2); d.Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and / or diastolic blood pressure ≥90 mmHg) or pulmonary hypertension or unstable angina; e. Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent surgery < 6 months prior to CNCT19 infusion; f. Clinically significant valvular disease; g. Other heart diseases that have been judged by the investigator to be unsuitable for receiving cell therapy.
- •Clinically significant pleural effusion.
- •Patients with a history of epilepsy, cerebrovascular ischemia / hemorrhage, cerebellar disease or other active central nervous system diseases.
- •History of deep vein thrombosis or pulmonary embolism within 6 months of screening.
- •Known history of hypersensitivity to ingredients used in the drug.
- •Has had treat with live vaccine within 6 weeks prior to screening.
- •Patients with evidence of currently uncontrollable serious active infections (e.g., sepsis, bacteremia, fungemia, viremia, etc.).
- •Life expectancy < 3 months.
- •Patient in other interventional clinical studies within 3 months before screening, who have received active drug therapy, or who intend to participate in another clinical trial or receive anti-tumor therapy outside the protocol during the entire study.
- •Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator.
研究组 & 干预措施
Single dose of CNCT19
Experimental
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.
干预措施: single dose of CNCT19 (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)
时间窗: 28 days
Determine the MTD and DLT of CNCT19 in the Treatment and recommend the dose for Phase II study.
Safety of CNCT19 therapy
时间窗: 24 months
Safety measures include adverse events as assessed by CTCAE v5.0.
次要结局
- Relapse-free survival (RFS)(24 Months)
- Overall survival (OS)(24 months)
- Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)(3 months)
- Overall Remission Rate (ORR)(6 months)
- Duration of remission (DOR)(24 months)
- Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow(6 months)
- Overall Remission Rate (ORR)(28 days)
- Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow(28 days)
- Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow(3 months)
研究者
研究点 (2)
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