Treatment of relapsed or refractory multiple myeloma using CAR-T cells

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

This study is testing a new CAR-T cell treatment for people with relapsed or refractory multiple myeloma who have already tried three or more therapies to see if it can help them.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, cyclophosphamide, fludarabine
• Locations: 1 site (Kunming, Kunming, Yunnan)
• Trial ID: NCT06515262 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of bispecific BCMA-GPRC5D CAR-T cells in patients with relapsed or refractory multiple myeloma who have undergone three or more lines of therapy. Participants will undergo a leukapheresis procedure to manufacture the CAR-T cells, followed by lymphodepleting therapy before the infusion of the modified T cells. The study is conducted at a single center and aims to assess the treatment's effectiveness and safety through follow-up evaluations.

Who should consider this trial

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

Not a fit: Patients who have not received the required prior therapies or are outside the age range 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.

How similar studies have performed: Other studies using CAR-T cell therapies for multiple myeloma have shown promising results, indicating potential success for this approach.

Eligibility criteria

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.

Where this trial is running

Kunming, Kunming, Yunnan

• Sanbin Wang — Kunming, Kunming, Yunnan, China (Recruiting)

Study contacts

• Principal investigator: Sanbin Wang — 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Study coordinator: Sanbin Wang, MD

Conditions Relapsed/Refractory Multiple Myeloma; BCMA-GPRC5D CAR-T