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
Overview
- Phase
- Phase 1
- Intervention
- HY004
- Conditions
- Non-hodgkin Lymphoma
- Sponsor
- Juventas Cell Therapy Ltd.
- Enrollment
- 80
- Primary Endpoint
- 【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
- Status
- Withdrawn
- Last Updated
- 8 months ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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;
Arms & Interventions
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.
Intervention: HY004
Outcomes
Primary Outcomes
【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)
Time Frame: 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)
Time Frame: 28 days
Determine the MTD and DLT of HY004 in the Treatment and recommend the dose for Phase II study.
Secondary Outcomes
- 【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)