Multiple Myeloma
Conditions
Brief summary
This study is an investigator-initiated single center, single arm clinical study with a target population of patients with relapsed/refractory multiple myeloma. It is an early exploratory clinical study of the safety, tolerability and initial efficacy of JY232 injection in the treatment of relapsed/refractory multiple myeloma.
Detailed description
This open-label, single-arm study is designed to evaluate the efficacy and safety of in vivo CAR-T cell therapy (JY232 Injection) in patients with relapsed/refractory multiple myeloma. Following screening, eligible subjects will provide informed consent and be enrolled in the study. They will then receive JY232 Injection via intravenous infusion. Subsequently, subjects will undergo safety and efficacy assessments for up to 24 months to evaluate disease control.
Interventions
DRUGJY232 Injection
This open-label, single-arm study is designed to evaluate the efficacy and safety of an in vivo Chimeric Antigen Receptor T-cell (CAR-T) therapy (JY232 preparation) in patients with relapsed or refractory multiple myeloma. Enrolled subjects will receive a single intravenous infusion of JY232, followed by a mandatory one-month in-hospital observation period for initial safety and efficacy assessments. Subsequently, subjects will enter a follow-up phase lasting up to 2 years to monitor long-term disease control.
Sponsors
Shenzhen Genocury Biotech Co., 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
1. The subject voluntarily signs the informed consent form, is willing and able to comply with all study requirements. 2. Age 18-75 years, male or female. 3. Diagnosis of active MM according to the diagnostic criteria established by the International Myeloma Working Group (IMWG). 4. Must have undergone stem cell transplantation (SCT) or be transplant-ineligible. 5. Must have received at least 2 prior lines of anti-MM therapy (including immunomodulatory drugs, proteasome inhibitors, and anti-Cluster of Differentiation 38 (CD38) therapy, as single agents or in combination. Patients who are intolerant or have contraindications to these therapies are eligible for enrollment if they meet other inclusion/
Exclusion criteria
). Each line of therapy must have included at least one complete cycle, and there must be documented evidence of disease progression on or relapse after the last line of therapy, or permanent discontinuation of therapy due to treatment-related toxicities (the reason for permanent discontinuation due to toxicity must be documented in the CRF). Furthermore, the patient must be refractory or intolerant to any established standard-of-care regimen that, in the investigator's assessment, is of significant clinical benefit to the patient. 6. The subject's tumor sample (bone marrow) tests positive for B-Cell Maturation Antigen (BCMA) expression on the plasma cell membrane via immunohistochemistry (IHC) or flow cytometry. 7. Presence of measurable disease at screening determined by any one of the following criteria: * Proportion of clonal plasma cells in bone marrow cytology, bone marrow biopsy histology, or flow cytometry ≥ 5%; * Serum monoclonal protein (M-protein) level: Immunoglobulin G (IgG) type M-protein ≥10 g/L; or Immunoglobulin A (IgA), Immunoglobulin D (IgD), Immunoglobulin E (IgE), Immunoglobulin M (IgM) type M-protein ≥5 g/L; * Urine M-protein level ≥200 mg/24 hours; * For MM without measurable serum or urine M-protein: involved serum free light chain ≥100 mg/L (10 mg/dL) and abnormal serum κ/λ free light chain ratio (\<0.26 or \>1.65); * Or clinical relapse: a. New bone lesions or soft tissue plasmacytomas (excluding osteoporotic fractures); b. Confirmed increase in Sum of the Product of Diameters (SPD) of existing plasmacytomas or bone lesions (≥50% increase in SPD of measurable lesions, absolute increase ≥1 cm). 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 (see Appendix 1 for ECOG scale). 9. Expected survival time ≥12 weeks. 10. The subject must have adequate organ function, meeting all the following laboratory results prior to enrollment: * Hematology: Absolute neutrophil count (ANC) ≥ 1×10\^9 /L (growth factor support is allowed, but must not have been administered within 7 days prior to the laboratory test); Absolute lymphocyte count (ALC) ≥0.3×10\^9 /L; Platelets ≥50×10\^9 /L (must not have received transfusion support within 7 days prior to the laboratory test); Hemoglobin ≥60 g/L (no red blood cell (RBC) transfusion within 7 days prior to the laboratory test; recombinant human erythropoietin is allowed); * Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN); Serum total bilirubin ≤1.5 × ULN; * Renal function: If available, measured CrCl from 24-hour urine collection; otherwise, calculated creatinine clearance (CrCl) via Cockcroft-Gault formula ≥ 40 ml/min; * Coagulation: Fibrinogen ≥1.0 g/L; Activated partial thromboplastin time (aPTT) ≤1.5 × ULN; Prothrombin time (PT) ≤1.5 × ULN; * Oxygen saturation \>91% (on room air); * Left ventricular ejection fraction (LVEF) ≥ 50 %; * No clinically significant pericardial effusion detected. 11. The subject and their spouse agree to use effective barrier or pharmacological contraception from signing the informed consent until one year after CAR-T cell infusion (excluding the rhythm method).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Related adverse events (AEs) | Up to 2 years after infusion | The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. |
| Maximum Tolerated Dose (MTD) | Up to 28 days after infusion | MTD will be determined based on Dose-Limiting Toxicities (DLTs ) observed during the first 28 days of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | Up to 3 months after infusion | The optimal degree of disease status improvement achieved by the patient over the course of the entire clinical trial or treatment period. |
| Duration of remission (DOR) | Up to 2 years after infusion | Duration of remission (DOR) is the time from the first detection of CR or PR to the discovery of Progressive Disease (PD). |
| Time To Progression (TTP) | Up to 2 years after infusion | The duration from the initiation of treatment until the first occurrence of objective disease progression. |
| Overall Response Rate (ORR) | Up to 3 months after infusion | Objective Response Rate (ORR) is defined as the proportion of subjects achieving stringent complete remission (sCR), complete remission (CR), very good partial response (VGPR) and partial response (PR). |
| Time to Complete Remission (TTCR) | Up to 2 years after infusion | The time interval from the subject's receipt of JY232 treatment to the first documentation of a complete remission (CR) of the disease. |
| Overall survival (OS) | Up to 2 years after infusion | Overall survival (OS) is the time from randomization to death from any cause. |
| Progression-free survival (PFS) | Up to 2 years after infusion | Progression-free survival (PFS) is the time between the time a patient with tumor disease receives treatment and the time between the observation of disease progression or death from any cause. |
| Minimal Residual Disease (MRD) | Up to 3 months after infusion | Flow cytometry-based MRD assessment, including the MRD-negative rate and duration of MRD negativity. |
Countries
China
Contacts
Primary ContactYing Zhao, Doctor
Outcome results
None listed