A Clinical Study to Evaluate the Safety and Efficacy of BCMA-GPRC5D CAR-T in Patients With Relapsed/Refractory Multiple Myeloma Who Received Three or More Lines of Therapy

• Status: Recruiting
• Trial end date: 2026-07-27
• Target enrollment: 0
• Participant gender: All

Summary

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D Chimeric antigen receptor (CAR) T-cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Wuhan Union Hospital, China
• Collaborator: Guangzhou Bio-gene Technology Co., Ltd
• Treatments: Cyclophosphamide; Fludarabine

Criteria

Inclusion Criteria:

1. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form;

2. Aged ≥ 18 years and ≤ 75 years;

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. Patients must recover from the toxicity of the last therapy (< grade 2 by CTCAE criteria);

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. Previous diagnosis and treatment of other malignancies within 3 years;

2. Patients received previous anti-tumor therapies before apheresis including following therapies: targeted therapies, epigenetics modulation drugs, other drugs or medical devices (invasive) of clinical trials, monoclonal antibodies, cytotoxic agents, PIs, IMiDs, radiotherapy;

3. Central Nervous System (CNS) involvement;

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. Patiens have severe systemic diseases or poor cardiovascular, liver, kidney functions;

8. Acute or chronic graft versus host disease (GvHD) occurs within 6 months before the screening or needs be treated with immunosuppressive agents;

9. Active autoimmune or inflammatory diseases of the nervous system;

10. Patients develop oncology emergencies and need to be treated before screening or infusion;

11. Uncontrolled infections that need antibiotics treatment;

12. Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis;

13. Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis;

14. 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;

15. Live attenuated vaccine within 4 weeks before screening;

16. Patients with severe mental illness;

17. Patients are addcited to alcohol or drugs;

18. Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion;

19. Other conditions considered inappropriate by the researcher.