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

Not Applicable

Recruiting

• Conditions: Relapsed/Refractory Multiple Myeloma

• Registration Number: NCT06515262
• Lead Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

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.

Study Timeline

• Status Verified: 2024-07
• Study Start: 2024-07-01
• Study First Submitted: 2024-07-17
• Study First Submitted QC: 2024-07-17
• Last Update Submitted: 2024-07-17
• Study First Posted: 2024-07-23
• Last Update Posted: 2024-07-23
• Primary Completion: 2026-11
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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).

Trial Locations

Locations (1)

Sanbin Wang; 🇨🇳 Kunming, Kunming, Yunnan, China