Dual-target BCMA–CD19 CAR-T therapy for relapsed or refractory multiple myeloma with extramedullary disease

Practical Clinical Study of Dual-targeting BCMA-CD19 CAR-T Cell Therapy for Extramedullary Infiltration in Refractory/Relapsed Multiple Myeloma

This trial will try a CAR-T treatment that targets both BCMA and CD19 for adults whose relapsed or refractory multiple myeloma has spread outside the bone marrow.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (Academic / other)
• Drugs / interventions: cyclophosphamide, fludarabine, CAR-T
• Locations: 1 site (Shanghai)
• Trial ID: NCT07003555 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, non-randomized, single-arm Phase 1 trial testing an autologous dual-target BCMA–CD19 CAR-T infusion in patients with relapsed or refractory multiple myeloma and measurable extramedullary lesions. Eligible participants must express BCMA on tumor cells and meet prespecified cardiac, liver, renal, coagulation, oxygenation, and pulmonary function thresholds. The primary focus is safety, with dose-limiting toxicity (DLT) and adverse event incidence and severity recorded within one month after infusion. Up to 18 participants will be enrolled and treated at participating centers in China.

Who should consider this trial

Good fit: Adults aged 18–75 with relapsed or refractory multiple myeloma, measurable extramedullary lesions, BCMA-positive tumor cells, and adequate organ function are the intended participants.

Not a fit: Patients who lack BCMA expression, have severe organ dysfunction, active uncontrolled infection, or who do not meet the CAR-T eligibility criteria are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the dual-target CAR-T could produce deeper or more durable remissions for patients with extramedullary, treatment-resistant multiple myeloma.

How similar studies have performed: BCMA-directed CAR-T therapies have shown high response rates in relapsed/refractory myeloma and smaller dual-target approaches including CD19 have been reported to help address antigen escape, so this builds on promising but still early evidence.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate in the trial and have good compliance.
2. Aged between 18 and 75 years old, regardless of gender.
3. Diagnosed with relapsed or refractory multiple myeloma according to the criteria of the International Myeloma Working Group (IMWG)2, and have measurable extramedullary lesions due to multiple myeloma.
4. Positive for BCMA in flow cytometry of bone marrow or cerebrospinal fluid tumor cells or immunohistochemistry of tumor tissue.
5. Organ functions: ① Cardiac function: Left ventricular ejection fraction \> 50% (by echocardiogram) in the past 2 weeks. ② Liver function: Alanine aminotransferase and aspartate aminotransferase \< 3 times the upper limit of normal (ULN). ③ Renal function: Creatinine clearance rate ≥ 40 mL/min (by Cockcroft and Gault formula). ④ Coagulation function: PT and APPT \< 1.5 times the ULN. ⑤ Arterial oxygen saturation (SpO₂) \> 95%. ⑥ Pulmonary function: FEV₁% predicted value ≥ 50%.
6. Female patients of childbearing age must have a negative serum pregnancy test at screening and before receiving cyclophosphamide and fludarabine or melphalan treatment; male patients should be willing to use effective contraceptive methods for 1 year after receiving the study treatment.
7. ECOG score ≤ 2.
8. Expected survival time \> 3 months.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Active infections that have not been effectively controlled.
3. Active autoimmune diseases that have not been effectively controlled.
4. Adverse reactions caused by previous treatments have not recovered to CTCAE grade ≤ 1.
5. For allogeneic transplant patients, active graft - versus - host disease (GVHD) that has not been effectively controlled.
6. Presence of any of the following: HBV - DNA copy number above the lower limit of detection; positive hepatitis C antibody (HCV - Ab) with HCV - RNA copy number above the lower limit of measurability; positive anti - Treponema pallidum antibody (TP - Ab); positive human immunodeficiency virus (HIV) antibody test.
7. Allergic or intolerant to fludarabine or cyclophosphamide.
8. Suffering from known symptomatic non - plasma cell infiltrative central nervous system diseases.
9. Uncontrollable cardiovascular and cerebrovascular diseases within 6 months, such as: a. New York Heart Association (NYHA) class III or IV congestive heart failure. b. Myocardial infarction occurred or coronary artery bypass grafting (CABG) was received ≤ 6 months before enrollment. c. Clinically significant ventricular arrhythmia or a history of unexplained syncope (excluding cases caused by vasovagal or dehydration). d. A history of severe non - ischemic cardiomyopathy.
10. A history of other untreated malignancies within the past 5 years or having other untreated malignancies concurrently.
11. The investigator assesses that the subject cannot or is unwilling to comply with the requirements of the study protocol.
12. Previous use of a CAR - T vector with the same structure.

Where this trial is running

Shanghai

• Shanghai Liquan Hospital — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Yao Yao

Conditions Relapsed or Refractory Multiple Myeloma