BG-CT-23-015

About this trial

Last updated a year ago

Study ID

BG-CT-23-015

Status

Recruiting

Type

Interventional

Phase

N/A

Placebo

Accepting

18 to 75 Years

All

Not accepting

Healthy Volunteers

Trial Timing

Started a year ago

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.

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.

Safety and Efficacy of Anti-BCMA-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM