Clinical trial NCT07003555: Dual-target BCMA-CD19 CAR-T Cell Therapy for RR/MM With Extramedullary Infiltration
Official title: Practical Clinical Study of Dual-targeting BCMA-CD19 CAR-T Cell Therapy for Extramedullary Infiltration in Refractory/Relapsed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Relapsed or Refractory Multiple Myeloma (RRMM)
Lead sponsor: Beijing GoBroad Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Liquan Hospital
First posted: 2025-06-04
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, non-randomized, single-arm clinical trial. Patients with relapsed/refractory multiple myeloma accompanied by extramedullary infiltration will receive BCMA - CD19 CAR-T cell therapy.

The primary objective is to prospectively evaluate the safety of dual-targeting BCMA and CD19 CAR - T cell therapy for extramedullary infiltration in relapsed/refractory multiple myeloma. The primary endpoints are to assess the type and incidence of dose-limiting toxicity (DLT) within one month after the infusion of BCMA-CD19 CAR-T cells in patients, as well as the incidence and severity of adverse events within one month after the infusion. It is expected that no more than 18 participants will be recruited.


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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: 30 days
measure: Adverse events (AEs）
timeFrame: 30 days
Secondary outcomes:
measure: Overall remission rate (ORR)
timeFrame: 90 days
measure: Event Free Survival (EFS)
timeFrame: from enrollment to the end of treatment at 2 years
measure: Duration of Response (DOR)
timeFrame: from enrollment to the end of treatment at 2 years
measure: Overall Survival (OS)
timeFrame: from enrollment to the end of treatment at 2 years
Other outcomes:
Locations:
Study officials:
References: