Evaluating a new CAR-T therapy for multiple myeloma patients who have not responded to previous treatments

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

This study is testing a new CAR-T therapy for people with multiple myeloma who haven't responded to other treatments to see if it can help them feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (other)
• Drugs / interventions: CAR-T, Chimeric antigen receptor
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT05998928 on ClinicalTrials.gov

What this trial studies

This clinical study is designed to assess the safety and efficacy of a bispecific CAR-T cell therapy targeting both BCMA and GPRC5D in patients with relapsed or refractory multiple myeloma who have undergone three or more lines of therapy. The study is open-label and single-arm, meaning all participants will receive the treatment without a control group. The therapy aims to improve clinical outcomes by targeting a broader range of multiple myeloma cells, especially those with low or absent BCMA expression. Participants will receive a combination of fludarabine, cyclophosphamide, and the BCMA-GPRC5D CAR-T cells.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with relapsed or refractory multiple myeloma who have received three or more lines of therapy.

Not a fit: Patients who have not been diagnosed with multiple myeloma or those who have not relapsed after previous treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat multiple myeloma, potentially improving their outcomes.

How similar studies have performed: While CAR-T therapies have shown promise in treating multiple myeloma, this specific bispecific approach is novel and has not been extensively tested in prior studies.

Eligibility 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.

Where this trial is running

Wuhan, Hubei

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (RECRUITING)

Study contacts

• Principal investigator: Heng Mei — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Study coordinator: Heng Mei

Conditions: Multiple Myeloma