Nanobody CAR-T cells targeting BCMA for treating relapsed multiple myeloma

A Multicenter Clinical Study on the Safety and Efficacy of Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of Relapsed/Refractory Multiple Myeloma

This study is testing a new type of CAR-T cell therapy that targets a specific protein in patients with relapsed multiple myeloma to see if it can improve their treatment outcomes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06503107 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of nanobody-based biepitope CAR-T cells that target BCMA in patients with relapsed or refractory multiple myeloma. The study is multicenter and open-label, enrolling 60 patients who will receive CAR-T cell therapy. Participants will be monitored for treatment safety, efficacy, duration of response, and long-term survival. The CAR-T cells are designed to recognize two different epitopes of the BCMA protein, aiming to enhance the killing of myeloma cells while minimizing inflammatory responses.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with relapsed or refractory multiple myeloma and positive BCMA expression in their myeloma cells.

Not a fit: Patients who have been treated with antibody-based drugs within two weeks prior to cell therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel and effective option for patients with relapsed or refractory multiple myeloma.

How similar studies have performed: Other studies have shown promise with CAR-T cell therapies targeting BCMA, indicating a potential for success with this novel approach.

Eligibility criteria

Inclusion Criteria:

* Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
* Aged ≥ 18 years and ≤ 75 years.
* Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG 2014).
* Diagnosed as relapsed/refractory disease or primary refractory disease; relapse is defined as disease progression within 60 days of the most recent treatment with three or more lines of therapy with different mechanisms of action; refractory is defined as failure to achieve MR or above efficacy with prior treatment and disease progression with recent treatment, or disease progression within 60 days of treatment.
* Flow cytometry or immunohistochemistry showed positive BCMA expression in myeloma cells.
* Have not been treated with antibody-based drugs within 2 weeks prior to cell therapy.
* ECOG score 0-2 points.
* HGB≥70g/L，PLT≥30×10\^9/L.
* Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Serum creatinine ≤ 1.5× ULN or creatinine clearance (Cockcroft-Gault) \>30 ml/min；
  2. Left ventricular ejection fraction (LVEF) ≥50%,
  3. Baseline peripheral oxygen saturation \> 90%;
  4. Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.

Exclusion Criteria:

* Previous diagnosis and treatment of other malignancies within 3 years;
* Presence of one of the following cardiac criteria: atrial fibrillation; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary QT prolongation, as judged by the investigator. Echocardiogram LVSF \<30% or LVEF \<50%; Clinically significant pericardial effusion; Cardiac insufficiency NYHA (New York Heart Association) III or IV (absence of this symptom confirmed by echocardiography within 12 months of treatment);
* Patients with active GVHD;
* Patients with a history of severe pulmonary impairment disease;
* Combined with other malignant tumors in the advanced stage;
* Co-infection with severe or persistent infection that cannot be effectively controlled;
* Combined with severe autoimmune disease or congenital immunodeficiency;
* Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA ≥ 500 IU/ml and abnormal liver function\] or hepatitis C antibody \[HCV-Ab\] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function);
* Human immunodeficiency virus (HIV) infection or syphilis infection;
* Patients with a history of severe allergy to biological products (including antibiotics);
* Patients with central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc;
* Pregnant or Lactating Women; Patients and his or her spouses have a fertility plan within 12 months after CAR-T cell infusion;
* Other conditions considered inappropriate by the researcher.

Where this trial is running

Wuhan, Hubei

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Mei Heng, M.D., Ph.D

Conditions Multiple Myeloma; CAR-T; BCMA; Relapsed / Refractory multiple myeloma