Dual-target CD19/BCMA CAR-T therapy for relapsed or refractory multiple myeloma

A Multicenter Clinical Study of Novel CD19/BCMA Dual-Targeted CAR-T Cell Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma

This study will try a CAR-T treatment that targets both CD19 and BCMA to see if it helps people whose multiple myeloma has returned or not responded to prior therapies.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: CAR-T, cyclophosphamide, fludarabine, Chimeric Antigen Receptor
• Locations: 1 site (Hangzhou)
• Trial ID: NCT07359014 on ClinicalTrials.gov

What this trial studies

This interventional trial gives patients an autologous CAR-T product engineered to recognize both CD19 and BCMA, building on preclinical data showing strong anti-myeloma activity. Eligible participants must have relapsed or refractory multiple myeloma with BCMA expression on plasma cells (≥30%) and have failed prior standard regimens such as proteasome inhibitors or lenalidomide. Bone marrow or plasmacytoma samples are centrally reviewed to confirm BCMA expression and patients receive lymphodepletion followed by the dual-target CAR-T infusion, with follow-up for safety and response. The study will collect safety, response, and durability data to determine whether this dual-target approach can produce deeper or more durable remissions than existing therapies.

Who should consider this trial

Good fit: Ideal candidates are adults with relapsed or refractory multiple myeloma who have BCMA expression ≥30%, have progressed after prior lines including bortezomib or lenalidomide, and are not pursuing or are ineligible/refuse HSCT.

Not a fit: Patients without sufficient BCMA expression, those eligible for and opting for immediate hematopoietic stem cell transplant, or those with rapidly progressing disease within 30 days of last therapy may not benefit from this trial.

Why it matters

Potential benefit: If successful, this dual-target CAR-T approach could produce deeper remissions and delay or prevent relapse in patients with heavily pretreated multiple myeloma.

How similar studies have performed: BCMA-targeted CAR-T therapies have produced high initial response rates but frequent relapses, and early dual-target CAR-T programs show promise in preclinical and early clinical reports though clinical proof of superiority is still limited.

Eligibility criteria

Inclusion Criteria:

1. Relapsed/refractory multiple myeloma.
2. Confirmed by immunohistochemistry (IHC) or flow cytometry of bone marrow samples: plasma cell membrane expression of BCMA is positive (≥30%); no requirement for CD19 positivity rate. All sites must centrally submit bone marrow or plasmacytoma biopsy specimens to the lead site's pathology department or bone marrow/liquid specimens to KingMed Diagnostics (third-party laboratory) for BCMA expression verification.
3. Relapsed/refractory patients must meet the following criteria:

   No response or disease progression after 3 cycles of bortezomib (proteasome inhibitor) or lenalidomide therapy No response or disease progression after 3 cycles of prior treatment regimen Interval between last treatment and disease progression \>30 days No current indication for hematopoietic stem cell transplantation (HSCT), or patient refusal of HSCT

   Definition of disease progression follows the 2021 International Myeloma Working Group (IMWG) criteria, meeting at least one of the following:

   Serum M protein ≥ 5 g/L Urine M protein ≥ 200 mg/24 h If serum free light chain (FLC) ratio is abnormal, patient FLC level ≥ 100 mg/L Biopsy-confirmed evaluable plasmacytoma Increased myeloplasmacytic percentage ≥25% (absolute increase ≥10%) Myeloplasm cells constitute ≥30% of total bone marrow cells
4. Expected survival \>12 weeks;
5. Disease status is evaluable and meets at least one of the following:

   Serum M-protein ≥10 g/L, 24-hour urine M-protein ≥ 200 mg, Serum FLC ≥ 50 mg/L, Plasmacytoma evaluable by imaging or laboratory testing, Bone marrow plasma cell percentage ≥ 30%
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
7. Sufficient venous access for apheresis or venipuncture, with no other contraindications to blood cell separation;
8. white blood cell (WBC) ≥ 1.5 × 10⁹/L; platelet (PLT) ≥ 45 × 10⁹/L.
9. Serum creatinine ≤ 1.5 times the upper limit of normal (ULN).
10. Alanine Aminotransferase (ALT) ≤ 2.5 ULN, Aspartate Aminotransferase (AST) ≤ 2.5 ULN.

All laboratory values within the above ranges must be achieved without ongoing supportive therapy.

Exclusion Criteria:

1. Received systemic therapy such as cyclophosphamide and fludarabine for lymphoma clearance within 2 weeks prior to enrollment or single-cell collection; prior CD19/BCMA CAR-T therapy; or cell or bispecific antibody therapy within 8 weeks prior to treatment.
2. Received bendamustine-containing regimens within 6 months prior to treatment.
3. Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV) positive status; any uncontrolled active infection, including active tuberculosis or Hepatitis B virus (HBV) DNA levels ≥1×10³ copies/mL.
4. Active infection within 72 hours prior to treatment initiation; subjects on ongoing prophylactic antibiotics, antifungals, or antivirals are not excluded provided there is no evidence of active infection and the antibiotics are not on the prohibited drug list.
5. Current systemic use of cyclosporine or steroids such as dexamethasone; recent or current use of inhaled steroids is not exclusionary.
6. Renal impairment with serum creatinine \>1.5 times the upper limit of normal (ULN).
7. Hepatic impairment with AST and/or ALT \>2.5 times ULN and direct bilirubin \>1.5 times ULN.
8. Hyponatremia, serum sodium \< 125 mmol/L.
9. Baseline serum potassium \< 3.5 mmol/L (exclusion not applied if potassium supplementation prior to study enrollment restores levels above this threshold).
10. Pregnant or lactating women.
11. Other serious conditions that may preclude participation in this trial (e.g., central nervous system disorders, severe heart failure, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina, gastric ulcer, active autoimmune disease, etc.).

Where this trial is running

Hangzhou

• Xuzhao Zhang — Hangzhou, China (Recruiting)

Study contacts

• Principal investigator: Wenbin Qian, Dr. — Second Affiliated Hospital, School of Medicine, Zhejiang University
• Study coordinator: Xuzhao Zhang

Conditions Relapse Multiple Myeloma; CAR-T therapy