A Multi-center, Open Label, Single-arm, Phase I/II Clinical Trial of HY004 Cell Injection in the Treatment of Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 80
- 主要终点
- 【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
研究概览
简要总结
This is a multi-center, open-label, single-arm, phase I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult patients with relapsed or refractory B-cell Non-Hodgkin's Lymphoma (r/r B-NHL).
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 in Adult(aged 18~75 years old) patients with r/r B-NHL.
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-NHL. 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-NHL. 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are willing to sign the informed consent form;
- •Aged 18-75 years, male or female;
- •Previously received≥2nd-line adequate therapy or hematopoietic stem cell transplantation (HSCT), and patients with CD19+/CD22+ relapsed/refractory B-NHL according to the WHO classification 2017, which are provided specifically as follows:
- •Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS);
- •Primary mediastinal large B cell lymphoma (PMBCL);
- •Grade 3b follicular lymphoma;
- •Transformed follicular lymphoma;
- •High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high grade B cell lymphoma - not otherwise specified.
- •Measurable imaging lesion at screening: Intranodal lesion must have a long diameter of more than 1.5 cm, and extranodal lesion must have a long diameter of more than 1.0 cm with PET-positive disease by Lugano classification .
- •PET-positive disease BY Lugano classification
- •Adequate bone marrow, renal, hepatic, pulmonary and cardiac function.
- •Adequate vascular access for leukapheresis procedure
- •Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.
排除标准
- •Active Central Nervous System (CNS) involvement by malignancy.
- •Patients with existing central nervous system disease or with a history of central nervous system disease.
- •Patients receiving any of the following drugs or therapies within the specified period prior to apheresis:
- •Alemtuzumab and Bendamustine within 6 months prior to apheresis;
- •Cladribine within 3 months prior to apheresis;
- •Lenalidomide within 1 mouth prior to apheresis;
- •Lymphocytotoxic chemotherapy within 2 weeks prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible;
- •Anti-CD20 monoclonal antibody and therapeutic dose of hormones within 7 d prior to apheresis;
- •Non-lymphocytotoxic chemotherapy within 7 d prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible;
- •Venetoclax (BCL-2 inhibitor) within 4 d prior to apheresis;
- •Idelalisib (PI3Kδ kinase inhibitor) within 2 d prior to apheresis;
- •DLI within 6 weeks prior to apheresis;
- •Radiotherapy within 6 weeks prior to apheresis - progressive disease at radiotherapy site, or PET positive lesion at other non-radiotherapy site is eligible;
- •Patients previously received CAR-T cell therapy, the products that have same indication and have beenlisted in China are eligible;
- •Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 mouths.
- •Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere 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.
- •History of cardiovascular disease.
- •Pregnant or nursing women.
研究组 & 干预措施
Single dose of HY004
Patients received a single dose of anti-CD22/CD19 CAR T cells after receiving a conditioning regimen of cyclophosphamide and fludarabine.
干预措施: HY004 (Biological)
结局指标
主要结局
【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
时间窗: 3 months
Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR.
【Phase I】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 HY004 in the Treatment and recommend the dose for Phase II study.
次要结局
- 【Phase I】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)(3 months)
- Complete Remission Rate (CRR)(3 months)
- Overall survival (OS)(24 mouths)
- Progression-free survival (PFS)(24 mouths)
- Event-free survival (EFS)(24 mouths)
- Safety of CNCT19 therapy: CTCAE v5.0(24 months)
- ORR（CR+PR）/CRR(6 months)
- Best Overall Response (BOR)(24 mouths)
- Duration of Remission (DOR)(24 mouths)