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

Non-hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06005649
• Other study ID #: HY004102
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: August 31, 2024
• Est. completion date: September 2026

Study information

• Verified date: March 2024
• Source: Juventas Cell Therapy Ltd.
• Contact: Junyin Yu
• Phone: +86 010-65960098
• Email: yujunyin[@]juventas.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: September 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 (PI3Kd 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-hodgkin Lymphoma

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Juventas Cell Therapy Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Prevalence and incidence of humoral immunogenicity to HY004.	To characterize the concentration of anti-drug antibodies	24 mouths
Primary	?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
Primary	?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	?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
Secondary	Safety of CNCT19 therapy: CTCAE v5.0	Safety measures include adverse events as assessed by CTCAE v5.0.	24 months
Secondary	Complete Remission Rate (CRR)	Efficacy of HY004 as measured by CR at 3 months after HY004 Cell Injection infusion.	3 months
Secondary	ORR(CR+PR)/CRR	Efficacy of HY004 as measured by ORR/CRR at 28 days after cell infusion.	28 days
Secondary	ORR(CR+PR)/CRR	Efficacy of HY004 as measured by ORR/CRR at 6 months after cell infusion.	6 months
Secondary	Best Overall Response (BOR)	The best overall response after HY004 infusion.	24 mouths
Secondary	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
Secondary	Progression-free survival (PFS)	PFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, or death for any reason.	24 mouths
Secondary	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
Secondary	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