Non-hodgkin Lymphoma
Conditions
Keywords
HY004, CD22/CD19 Chimeric Antigen Receptor T-cells
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.
Interventions
BIOLOGICALHY004
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
Sponsors
Juventas Cell Therapy Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 【Phase II】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR) | 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) | 28 days | Determine the MTD and DLT of HY004 in the Treatment and recommend the dose for Phase II study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of CNCT19 therapy: CTCAE v5.0 | 24 months | Safety measures include adverse events as assessed by CTCAE v5.0. |
| Complete Remission Rate (CRR) | 3 months | Efficacy of HY004 as measured by CR at 3 months after HY004 Cell Injection infusion. |
| ORR（CR+PR）/CRR | 28 days | Efficacy of HY004 as measured by ORR/CRR at 28 days after cell infusion. |
| Best Overall Response (BOR) | 24 mouths | The best overall response after HY004 infusion. |
| 【Phase I】Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR) | 3 months | Efficacy of HY004 as measured by ORR at 3 months after HY004 Cell Injection infusion, which includes CR and PR. |
| Progression-free survival (PFS) | 24 mouths | PFS means duration from the HY004 Cell Injection infusion to progression of lymphoma, or death for any reason. |
| Event-free survival (EFS) | 24 mouths | 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. |
| Overall survival (OS) | 24 mouths | 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. |
| Duration of Remission (DOR) | 24 mouths | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| In vivo cellular Pharmacokinetic (PK) profile of HY004. | 24 mouths | 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. |
| Prevalence and incidence of humoral immunogenicity to HY004. | 24 mouths | To characterize the concentration of anti-drug antibodies |
| In vivo cellular pharmacodynamics (PD) profile of HY004. | 3 mouths | To characterize the concentration of cytokines ,including Interleukin-6(IL-6) at least in Serum. |
Outcome results
None listed