CAR19BCMA CAR-T Cells for the Treatment of R/R Plasma Cell Neoplasms

Official title

A Clinical Study on the Safety and Efficacy of CAR19-BCMA Dual-target CAR-T Cell Therapy for Relapsed/Refractory Plasma Cell Neoplasms

Overview

This is a single arm study to evaluate the safety and efficacy of CAR19BCMA CAR-T cells in the treatment of relapsed/refractory CD19/BCMA positive plasma cell neoplasms.

Detailed description

This study is an exploratory clinical trial of a single-arm, open, single-center treatment of CAR19BCMA CAR-T cell. 20 subjects with relapsed or refractory CD19/ BCMA positive positive plasma cell neoplasms will be enrolled and received CAR19BCMA CAR T cells injection therapy, and related data such as adverse reactions and therapeutic effects after medication were followed up. To evaluate its safety and efficacy

Interventions

• Other CAR19BCMA-T cells
  CAR19BCMA-T cells Each subject will be infused with single dose of CD19BCMA-CAR-T cells. A classic "3+3" dose escalation will be employed. The low dose is 1×10\^6 /kg, the medium dose is 2×10\^6 /kg, and the high dose is 3×10\^6 /kg. Drug: fludarabine and cyclophosphamide Drug: Fludarabine Fludarabine will be given at a dose of 30 mg/m2/day intravenously (IV) for 3 days prior to the infusion of CD19BCMA-CAR-T cells. Drug: Cyclophosphamide Cyclophosphamide will be given at a dose of 300 mg

Primary outcome measures

• According to the incidence of treatment-related adverse events (AEs) to evaluate the safetyof CAR19BCMA CAR-T cells in the treatment of relapsed/refractory CD19+BCMA+plasma cell neoplasms. [Time frame: up to 3 years]
• According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safety of CAR19BCMA CAR-T cells in the treatment of relapsed/refractory CD19+BCMA+ plasma cell neoplasms. [Time frame: MTD will be determined based on DLTs observed during the first 28 days of study treatment]

Secondary outcome measures (1)

• According to the objective response rate (ORR) to evaluate the efficacy of CAR19BCMA CAR-T cells in the treatment of relapsed/refractory CD19+BCMA+ plasma cell neoplasms. [Time frame: Within 3 months following infusion of CAR19BCMA CAR-T cells]

Eligibility criteria

Inclusion criteria

• Relapsed/refractory CD19BCMA positive plasma cell neoplasms must be assured and meet all of the following conditions:

1.1 Confirmation for either BCMA or CD19 positivity using immunohistochemistry or flow cytometry.

1.2 Patients with multiple myeloma, plasma cell carcinoma, and plasma cell leukemia who have received at least three 3 lines treatment (including anti-CD38 monoclonal antibodies, protease inhibitors, immunosuppressants, etc.) but have failed or experienced relapse.

1.3 Patients with system light chain amyloidosis who have received at least 2 lines treatments in the past \[anti-CD38 monoclonal antibody, proteasome inhibitor (PI), or immunomodulatory drug (IMiD)\], but have failed or experienced relapse.

• Age 18-75 years,
• no gender restrictions;
• ECOG score ≤ 2 points;
• Expected survival period is not less than 3 months;
• HGB≥60g/L;
• Liver and kidney function and cardiopulmonary function meet the following requirements: (1) Creatinine ≤ 2× ULN; (2)left ventricular ejection fraction≥50%; (3) Oxygen saturation >90%; (4)Total bilirubin ≤1.5×ULN, ALT and AST≤2.5×ULN;
• Participants agreed to use contraception from the time of informed consent until 1 year after CAR-T cell infusion.

Exclusion criteria

• Severe heart failure with left ventricular ejection fraction <50%;
• A history of severe lung function impairment; Combined with other advanced malignant tumors;
• Complicated with severe infection that could not be effectively controlled;
• Severe autoimmune disease or congenital immune deficiency;
• Active viral hepatitis (defined as positive hepatitis B virus DNA \[HBV-DNA\] or hepatitis C virus RNA \[HCV-RNA\] detection, with test results exceeding the lower limit of quantification); Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection;
• History of severe allergy to biological products (including antibiotics);
• Allogeneic hematopoietic stem cell transplant patients who still have an acute graft-versus-host response (GVHD) one month after discontinuation of immunosuppressants;
• Patients with other serious physical or mental illnesses or laboratory abnormalities that could increase the risk of participating in the study or interfere with the results of the study, and those who were deemed by the investigator to be unsuitable for participation in the study;
• Female patients (those with fertility) are in pregnancy or lactation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• The Four Medical Center of PLA General Hospital, China — Beijing
• The Six Medical Center of PLA General Hospital, China — Beijing

Identifiers

NCT: NCT07077330 · 2025-653-01 · 2025KY072-KS001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗