CAR-T therapy targeting BCMA and GPRC5D for relapsed multiple myeloma

BCMA-GPRC5D CAR-T Therapy in Relapsed or Refractory Multiple Myeloma：A Prospective, Single-center, Single-arm Phase I/IIa Clinical Trial

This study is testing a new CAR-T therapy that targets two specific proteins to see if it can help people with relapsed multiple myeloma who haven't responded well to other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shenzhen University General Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, prednisone, CAR T
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT06644443 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of a novel CAR-T therapy that targets both BCMA and GPRC5D in patients with relapsed or refractory multiple myeloma. The approach aims to address the limitations of existing BCMA-targeted therapies, particularly for patients with low or negative BCMA expression. Participants will receive CAR-T cells engineered to target both antigens, potentially improving treatment outcomes. The study will assess the response rates and safety profile of this dual-target therapy in a clinical setting.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with relapsed or refractory multiple myeloma who have previously failed standard therapies.

Not a fit: Patients with early-stage multiple myeloma or those who have not undergone prior treatment 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: While CAR-T therapies have shown promise in treating multiple myeloma, this specific dual-target approach is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 (≥ 18 years old, ≤ 75 years old), gender is not limited;
2. The subject voluntarily participates in the research and signs the \"Informed Consent\" by himself or his legal guardian;
3. Definitely diagnosed as relapsed or refractory multiple myeloma: use chemotherapy regimens containing bortezomib, or chemotherapy regimens containing lenalidomide, the treatment is ineffective, or the disease progresses within 60 days after the end of the last chemotherapy;
4. The patient has one or more measurable multiple myeloma lesions, which must include any of the following:1) Serum M protein is greater than or equal to 0.5g / dl (10g / l) 2) Urine M protein is greater than or equal to 200 mg / 24 h serum FLC ratio is abnormal 3) Serum free light chain (FLC) ≧5 mg / dL (50 mg /L) 4) Plasmacytoma that can be measured by physical examination or imaging examination 5) Myeloma cells in bone marrow ≧10% by flow cytometry or immunohistochemical examination
5. After flow cytometry or immunohistochemical examination, myeloma cells have positive BCMA and GPRC5D expression;
6. No salvage chemotherapy was used within 4 weeks before cell therapy;
7. No antibody drug therapy was used within 2 weeks before cell therapy;
8. The ECOG score is 0-2 points;
9. The subject has no contraindications to peripheral blood apheresis;
10. The expected survival period is ≧12 weeks;
11. Female subjects of childbearing age must have a negative urine pregnancy test within 7 days prior to cell therapy and not during the lactation period; female or male subjects of childbearing age must take effective contraceptive measures throughout the study

Exclusion Criteria:

1. Those who have a history of allergies to any of the ingredients in cell products;
2. The following conditions in laboratory tests: including but not limited to serum total bilirubin ≥ 1.5 mg/dl; serum ALT or AST greater than 2.5 times the upper limit of normal; blood creatinine ≥ 2.0 mg/dl; hemoglobin\<80g/l; does not rely on GCSF or other growth factors, the absolute neutrophil count is less than 1000 / mm3; no blood transfusion is required, and the platelet count is less than 30,000 / mm3;
3. According to the New York Heart Association (NYHA) cardiac function classification standards, patients with grade III or IV cardiac insufficiency; or echocardiographic examination of left ventricular ejection fraction (LVEF) \<50%;
4. Abnormal lung function, blood oxygen saturation in indoor air\<92%;
5. Myocardial infarction, cardiovascular angioplasty or stenting, unstable angina, or other serious clinical heart diseases within 12 months before enrollment;
6. Hypertension is grade 3 and the blood pressure is not well controlled by medication;
7. Patients with prolonged QT interval on ECG, patients with severe heart disease such as severe arrhythmia in the past;
8. Previously suffering from head injury, disturbance of consciousness, epilepsy, more serious cerebral ischemia or cerebral hemorrhage disease;
9. Need to use any anticoagulant (except aspirin);
10. Patients who need urgent treatment due to tumor progression or spinal cord compression;
11. Patients with CNS metastasis or CNS involvement symptoms (including cranial neuropathy and extensive disease or spinal cord compression);
12. The investigator determines that there are serious complications or diseases that increase the risk of the subject or affect the research, including but not limited to, for example: liver cirrhosis, recent major trauma, etc.;
13. After allogeneic hematopoietic stem cell transplantation;
14. Plasma cell leukemia;
15. Before apheresis and within 2 weeks before CAR-T cell infusion, apply more than 5 mg/d of prednisone (or an equivalent amount of other corticosteroids);
16. Patients with autoimmune diseases, immunodeficiencies or other patients who need immunosuppressive therapy;
17. There is an uncontrolled active infection;
18. Live vaccination within 4 weeks before enrollment;
19. HIV, HBV, HCV and TPPA/RPR infected persons, and HBV carriers;
20. The subject has a history of alcoholism, drug abuse or mental illness;
21. The subject has participated in any other clinical research within 3 months before joining this clinical research;
22. The researcher believes that the subjects have other conditions that are not suitable for participating in this study.

Where this trial is running

Shenzhen, Guangdong

• Shenzhen University General Hospital — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Xiao Guo, Doctor — Shenzhen University General Hospital
• Study coordinator: Xiao Guo, Doctor

Conditions Multiple Myeloma in Relapse; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders