Multiple Myeloma
Conditions
Keywords
CAR-T, GPRC5D, Multiple Myeloma
Brief summary
This is a single-arm, open-label, dose-escalation study to evaluate the safety, tolerability, cellular kinetics and initial efficacy of CAR-T cell therapy targeting GPRC5D in multiple myeloma subjects who have failed the standard treatments.
Interventions
DRUGGPRC5D-CAR-T
After enrollment, subjects complete the PBMC apheresis, then complete the Lymphocyte clearance, and then receive the dose climbing test: 1×10e6/kg，3×10e6/kg，6×10e6/kg.
Sponsors
OriCell Therapeutics Co., Ltd.
Zhejiang University
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 can understand and have the ability to sign an informed consent form; 2. Male or female subjects, aged 18-75 years; 3. The expected survival period is not less than 12 weeks; 4. ECOG score ≤ 2 ; 5. Diagnosed as multiple myeloma according to the IMWG standard in 2018; 6. The expression of GPRC5D in bone marrow plasma cells is more than 20%, or it is positive in tumor tissue by immunohistochemistry. One of the following criteria must be detected: 1. If IgG type MM, serum M protein ≥10g/L; if IgA, IgD, IgE or IgM type MM, serum M protein ≥5g/L; 2. Or urine M protein level ≥200mg/24h; 3. Or light chain type MM, serum free light chain (sFLC) ≥ 100mg / L and K/ λ FLC ratio is abnormal; 4. Or there are extramedullary lesions; 7. Subjects who have received at least 3 different mechanism drugs (including chemotherapy, protease inhibitors, immunosuppressive agents, etc.) have failed treatments, or have progressed or recurred during the last treatment or within 6 months after the end of treatment ; 8. Lung function is normal, and oxygen saturation is greater than 92%; 9. No heart disease or coronary heart disease, echocardiogram showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no serious arrhythmia; 10. Liver function: TBIL\<3×ULN, AST\<2.5×ULN, ALT\<2.5ULN; 11. Renal function: creatinine clearance rate (estimated by Cockcroft Gault formula) ≥ 30 mL/min; 12. The blood routine meets the following standards: 1. Lymphocyte count\>0.5×10e9/L; 2. Neutrophils ≥1.0×10e9/L; 3. Hemoglobin ≥80g/L; 4. Platelet ≥75×10e9/L 13. From the use of study drug to 2 years after treatment, male subjects or female subjects of childbearing age must agree and be able to take effective contraceptive measures.
Exclusion criteria
1. Pregnant or breastfeeding; 2. HBsAg or HBcAb are positive, and the quantitative detection of HBV DNA in peripheral blood is more than 100 copies / L; HCV antibody and HCV RNA in peripheral blood are positive; HIV antibody positive; Syphilis antibody is positive in the first screening; 3. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade III), severe arrhythmia with poor drug control, liver, kidney or metabolic diseases; 4. Had hypersensitivity or intolerance to any drug used in this study; 5. Patients who received anti-cancer chemotherapy or other medications within 2 weeks before screening; 6. Uncontrolled malignant tumors except MM, excluding malignant tumors that received radical treatment and no active disease was found within 3 years before enrollment; 7. Clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis; 8. In the past two years, autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs, or required systemic application of immunosuppressive or other drugs; 9. Severe active viral, bacterial or uncontrolled systemic fungal infections; Hereditary bleeding / coagulation diseases, history of non traumatic bleeding or thromboembolism, other diseases that may increase the risk of bleeding, etc; 10. Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during the study period; 11. Patients received allogeneic stem cell therapy; 12. Any unsuitable to participate in this trial judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limited toxicity (DLT) | From date of initial treatment to Day 28 post GPRC5D CAR-T infusion. | Dose limited toxicity |
| AE and SAE | From admission to the end of the follow-up, up to 2 years | Adverse event and serious adverse event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate, DCR | From Day 28 GPRC5D CAR-T infusion up to 2 years | The percentage of patients with remission and stable disease after treatment in the total evaluable cases. |
| Duration of remission, DOR | 24 months post GPRC5D CAR-T cells infusion | The time from the first assessment of remission or partial remission of the tumor to the first assessment of disease progression or death from any cause; |
| Concentration of CAR-T cells | From admission to the end of the follow-up, up to 2 years | In peripheral blood and bone marrow |
| Overall survival, OS | From GPRC5D CAR-T infusion to death，up to 2 years | The time from the cell reinfusion to death due to any cause. |
| Progression-free survival, PFS | 24 months post GPRC5D CAR-Tcells infusion | The time from cell reinfusion to the first assessment of tumor progression or death from any cause |
| Objective Response Rate, ORR | In 3 months of GPRC5D CAR-T cell infusion | Proportion of subjects with complete or partial remission |
Countries
China
Outcome results
None listed