A Phase I/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of HY004 in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 50
- 主要终点
- Overall Remission Rate (ORR)
研究概览
简要总结
This is a multi-center, phase I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult 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 I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult (aged 18~65 years old) patients with r/r B-cell ALL.
The phase I part of the trial is to evaluate the safety, optimal dose of HY004, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Adult patients with r/r B-cell ALL. The phase II part of the trial is to evaluate the efficacy and safety of HY004 in in the treatment of Adult patients with r/r B-cell ALL. The study includes screening, pre-treatment (Cell Product manufacture & lymphodepletion), HY004 infusion, safety and efficacy follow-up, and survival follow-up. All subjects who have received HY004 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
- 18 Years 至 65 Years（Adult, Older 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);
- •Gender is not limited, and the age at the time of screening is ≥ 18 years old and ≤ 65 years old;
- •Relapsed or refractory acute lymphoblastic leukemia (ALL);
- •Documentation of CD19 and/orCD22 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening;
- •Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening;
- •ECOG score 0-1 points;
- •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;
- •History of concomitant genetic syndrome;
- •Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD within 4 weeks before screening; Patients with a history of allogeneic hematopoietic stem cell transplantation within 12 weeks before single collection;
- •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 have used CAR-T cell therapy before screening;
- •Patients with an expected lifespan of less than 3 months.
研究组 & 干预措施
Participant Group
Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m^2 intravenously [IV] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).
干预措施: HY004 (Biological)
Participant Group
Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m^2 intravenously [IV] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).
干预措施: Cyclophosphamide (Drug)
Participant Group
Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m^2 intravenously [IV] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).
干预措施: Fludarabine Phosphate (Drug)
结局指标
主要结局
Overall Remission Rate (ORR)
时间窗: at the end of Month 3
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
- Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity(at the end of Month 3)
- Duration of remission (DOR)(to data cutoff date)
- Allogeneic Stem Cell Transplant (Allo-SCT) rate(First infusion date of HY004 to data cutoff date(up to 2 years))
- Relapse Free Survival (RFS)(up to 2 years)
- Overall survival (OS)(2 years)
- Overall Remission Rate (ORR)(within 3 months)
- Event-Free Survival(EFS)(up to 2 years)
- Best overall response (BOR)(up to 2 years)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events（TEAE）(up to 2 years)