Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
BCMA-GPRC5D CAR-T
Brief summary
This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D CAR-T cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.
Detailed description
This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D CAR-T cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.A leukapheresis procedure will be performed to manufacture Anti-BCMA-GPRC5D chimeric antigen receptor (CAR) modified T cells. Prior to Anti-BCMA-GPRC5D CAR-T cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T therapy was evaluated by investigators.
Interventions
BIOLOGICALAnti-BCMA-GPRC5D CAR-T cells infusion
Subiects who meet the enrollment conditions will receive intravenous infusion of anti-BCMA-GPRC5D CAR-T Cells after lymphodepleting therapy.
Sponsors
Guangzhou Bio-gene Technology Co., Ltd
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
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 patient or his/her guardian understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure; 2. Age 18-75 years old, gender unlimited; 3. Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG); 4. The presence of measurable disease at screening meets one of the following criteria:Serum M-protein ≥ 1.0 g/dL or Urine M-protein ≥ 200 mg/24h or diagnosed as Light-chain MM without measurable disease in serum and urine; Serum free light chain ≥ 10 mg/dL with an abnormal κ/λ ratio; 5. Patients must relapse or be refractory after three or more lines of therapy, which at least include: one Proteasome Inhibitor (PI), one Immunomodulatory Drug (IMiD), and one anti-CD38 monoclonal antibody; 6. diagnosed as relapsed/refractory disease or primary refractory disease; 7. The last treatment is ineffective, or the disease progresses within 60 days after the end of the last therapy; 8. The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade \< 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy); 9. ECOG score 1-2 points and the expected survival period ≥ 3 months; 10. Liver, kidney and cardiopulmonary functions meet the following requirements: 1. Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN; 2. Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min; 3. Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days; 4. Baseline peripheral oxygen saturation \> 92%; 5. Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic) calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L); 6. Left ventricular ejection fraction (LVEF) \> 45%, without confirmed pericardiac effusion and abnormal electrocardiography with clinical significance; 7. Without clinically significant pleural effusion; 11. Venous access could be established; without contraindications of apheresis.
Exclusion criteria
1. Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma; 2. Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter; 3. It is suspected that MM has involved the central nervous system or meninges and has been confirmed by MRI or CT, or there are other active central nervous system diseases; 4. Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL, amyloidosis; 5. Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of detection of the research institution; EBV DNA titer is higher than the lower limit of detection of the research institution; 6. Patients have a severe allergic history; 7. 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 \[New York Heart Association (NYHA) classification ≥ grade III\]; 8. Systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment; 9. Patients with acute/chronic graft-versus-host disease (GVHD) or requiring immunosuppressive therapy for GVHD within 6 months prior to screening; 10. Active autoimmune or inflammatory diseases of the nervous system; 11. Patients develop oncology emergencies and need to be treated before screening or infusion; 12. Uncontrolled infections that need antibiotics treatment; 13. Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis; 14. Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis; 15. Patients receive a major surgical operation within 4 weeks before lymphodepletion or do not recover completely before the enrollment; or plan to receive a major surgical operation during the study period; 16. Live attenuated vaccine within 4 weeks before screening; 17. Persons with serious mental illness; 18. Alcoholics or persons with a history of drug abuse; 19. Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion; 20. Any unsuitable to participate in this trial judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events(AE) after infusion | within 2 years after infusion | The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | within 2 years after infusion | Overall Response Rate (ORR) is defined as the proportion of subjects achieving strict complete remission(sCR), complete response(CR), very good partial response(VGPR） and partial response(PR). |
| Concentration of CAR-T cells | Days 1,4, 7, 10, 14 ,21,28and months 2, 3, 6, 9, 12,18,24 after infusion | Concentration of CAR-T cells measured by Flow cytometry after CAR-T infusion |
| Progression-free survival(PFS) | within 2 years after infusion | Progression-free survival(PFS) refers to the time from cell reinfusion to the first assessment of tumor progression or death from any cause. |
| Overall survival(OS) | within 2 years after infusion | Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-T cells until death (from any cause). |
Countries
China
Contacts
Primary ContactSanbin Wang, MD
Backup ContactSanbin Wang, MD
Outcome results
None listed