Clinical Trial of HY004 Cell Injection in the Treatment of Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Non-hodgkin Lymphoma
• Intervention / Treatment: Biological: HY004

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Patients who are willing to sign the informed consent form;
2. Aged 18-75 years, male or female;

3. 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:

   1. Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS);
   2. Primary mediastinal large B cell lymphoma (PMBCL);
   3. Grade 3b follicular lymphoma;
   4. Transformed follicular lymphoma;
   5. High grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high grade B cell lymphoma - not otherwise specified.
4. 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 .
5. PET-positive disease BY Lugano classification
6. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function.
7. Adequate vascular access for leukapheresis procedure
8. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.

Key Exclusion Criteria:

1. Active Central Nervous System (CNS) involvement by malignancy.
2. Patients with existing central nervous system disease or with a history of central nervous system disease.

3. Patients receiving any of the following drugs or therapies within the specified period prior to apheresis:

   1. Alemtuzumab and Bendamustine within 6 months prior to apheresis;
   2. Cladribine within 3 months prior to apheresis;
   3. Lenalidomide within 1 mouth prior to apheresis;
   4. Lymphocytotoxic chemotherapy within 2 weeks prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible;
   5. Anti-CD20 monoclonal antibody and therapeutic dose of hormones within 7 d prior to apheresis;
   6. Non-lymphocytotoxic chemotherapy within 7 d prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible;
   7. Venetoclax (BCL-2 inhibitor) within 4 d prior to apheresis;
   8. Idelalisib (PI3Kδ kinase inhibitor) within 2 d prior to apheresis;
   9. DLI within 6 weeks prior to apheresis;
   10. Radiotherapy within 6 weeks prior to apheresis - progressive disease at radiotherapy site, or PET positive lesion at other non-radiotherapy site is eligible;
4. Patients previously received CAR-T cell therapy, the products that have same indication and have beenlisted in China are eligible;
5. Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 mouths.
6. Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD within 4 weeks before screening.
7. Active systemic autoimmune disease.
8. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti- HCV positive).
9. Patients with active infections at screening.
10. History of cardiovascular disease.
11. Pregnant or nursing women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: HY004; Autologous 2nd generation bispecific CAR-T cells targeting both CD22 and CD19, single infusion intravenously. Start Dose level: 2.00 x 10^6/kg CAR+T-cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
【Phase I】Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)	Determine the MTD and DLT of HY004 in the Treatment and recommend the dose for Phase II study.	28 days
【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)	Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CNCT19 therapy: CTCAE v5.0	Safety measures include adverse events as assessed by CTCAE v5.0.	24 months
【Phase I】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)	Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR.	3 months
Complete Remission Rate (CRR)	Efficacy of HY004 as measured by CR at 3 months after HY004 Cell Injection infusion.	3 months
ORR（CR+PR）/CRR	Efficacy of HY004 as measured by ORR/CRR at 28 days after cell infusion.	28 days
ORR（CR+PR）/CRR	Efficacy of HY004 as measured by ORR/CRR at 6 months after cell infusion.	6 months
Best Overall Response (BOR)	The best overall response after HY004 infusion.	24 mouths
Duration of Remission (DOR)	DOR means the duration from reaching the response (e.g., CR or PR) criteria of the therapy to the first, clearly defined progressive disease, or death for disease under investigation.	24 mouths
Progression-free survival (PFS)	PFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, or death for any reason.	24 mouths
Event-free survival (EFS)	EFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, start of new anti-cancer treatment, relapse, death of any cause or discontinued due to any adverse events.	24 mouths
Overall survival (OS)	OS is defined as the time from the signing of informed consent form to the date of the last survival follow-up or death due to any cause.	24 mouths

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
In vivo cellular Pharmacokinetic (PK) profile of HY004.	To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in blood by quantitative polymerase chain reaction(qPCR) and Flow Cytometry.	24 mouths
In vivo cellular pharmacodynamics (PD) profile of HY004.	To characterize the concentration of cytokines ,including Interleukin-6(IL-6) at least in Serum.	3 mouths
Prevalence and incidence of humoral immunogenicity to HY004.	To characterize the concentration of anti-drug antibodies	24 mouths

Collaborators and Investigators

• Sponsor: Juventas Cell Therapy Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: August 17, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: HY004; CD22/CD19 Chimeric Antigen Receptor T-cells
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: HY004102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No