A Phase Ib/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of CNCT19 in Children and Adolescent(Pediatric) Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 47
- 试验地点
- 9
- 主要终点
- Overall Remission Rate (ORR)
研究概览
简要总结
This is a multi-center, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 treatment in Children and Adolescent (pediatric) patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-cell ALL).
详细描述
This trial is a multi-center, open label, single-arm, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 in Children and Adolescent(aged 3~18 years old) patients (pediatric) with r/r B-cell ALL.
The phase Ib part of the trial is to evaluate the safety, optimal dose of CNCT19, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Children and Adolescent patients with r/r B-cell ALL.
The phase II part of the trial is to evaluate the efficacy and safety of CNCT19 in in the treatment of Children and Adolescent patients with r/r B-cell ALL.
The study includes screening, pre-treatment (Cell Product manufacture & lymphodepletion), CNCT19 infusion , safety and efficacy follow-up, and survival follow-up. All subjects who have received CNCT19 infusion will be followed for up to 2 years.
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
- 3 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian)
- •Weight ≥10kg
- •Relapsed or refractory acute lymphoblastic leukemia (ALL).
- •Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening.
- •Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
- •Karnofsky (age ≥ 16 years) performance status ≥ 70 or Lansky (age < 16 years) performance status ≥ 50 at screening
- •Organ function requirements: All patients must have adequate renal and liver functions
排除标准
- •Active Central Nervous System (CNS) involvement by malignancy.
- •Isolated extra-medullary disease relapse.
- •Patients with Burkitt's lymphoma/leukemia, mixed phenotypic acute leukemia and Chronic Myelogenous Leukemia in Blast Crisis
- •History of concomitant genetic syndrome
- •Patients with acute graft-versus-host disease (GVHD) or moderate-to-severe chronic GVHD within 4 weeks before screening.
- •Active systemic autoimmune disease
- •Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive).
- •Patients with active infections at screening.
- •Patients who received specified chemotherapy before CNCT19 infusion
- •Radiotherapy before CNCT19 infusion:
- •Non-CNS site of radiation completed < 4 weeks prior to CNCT19 Infusion; CNS directed radiation completed < 8 weeks prior to CNCT19 infusion.
- •Donor lymphocyte infusion (DLI) must be stopped > 6 week prior to CNCT19 infusion.
- •Has had treatment with any prior CAR-T therapy.
- •Life expectancy < 3 months.
研究组 & 干预措施
Single dose of CNCT19
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
Overall Remission Rate (ORR)
时间窗: within 3 months
ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification, as determined by Independent Review Committee (IRC)
次要结局
- Pharmacokinetic (PK)- Cmax of CNCT19(Up to 2 years)
- Duration of remission (DOR)(to data cutoff date)
- Allogeneic Stem Cell Transplant (Allo-SCT) rate(First infusion date of CNCT19 to data cutoff date(up to 2 years))
- Relapse Free Survival (RFS)(2 years)
- Overall complete Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators(within 3 months)
- In vivo cellular Pharmacokinetic (PK) profile of CNCT19(Up to 3 months(BM sample); Up to 2 years(Blood sample))
- Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators(at the end of Month 3)
- Best overall response (BOR)(up to 2 years)
- Percentage of participants with anti-CNCT19 antibodies in serum(2 years)
- Treatment-Emergent Adverse Events(up to 2 years)
- Overall survival (OS)(2 years)
- Concentration of Cytokines in Serum(28 days)
- Overall Remission Rate (ORR) as determined by IRC and Investigators(at the end of month 3)
- Pharmacokinetic (PK)- Tmax of CNCT19.(Up to 2 years)
- Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities(From CNCT19 infusion to date of data cutoff (maximum: 2 years))
- Pharmacokinetic (PK)- AUC of CNCT19.(Up to 2 years)