Autologous BCMA-targeted CAR-T Cell Injection for Relapsed/Refractory Light Chain Amyloidosis
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorBeijing Boren Hospital
About this trial
Systemic light chain amyloidosis (AL amyloidosis) is the most common type of systemic amyloidosis, with diverse clinical manifestations and difficulties in diagnosis and treatment. AL amyloidosis may involve multiple organs; the kidney and heart are the most commonly involved organs. The treatment goal is to reduce monoclonal immunoglobulin light-chain levels, prevent further amyloid deposition in important organs, and alleviate or reverse organ dysfunction caused by amyloid deposition. The principal approach to achieve this goal is to eliminate the plasma-cell or B-cell clones producing abnormal light chains. For patients with relapsed/refractory AL amyloidosis, the protocol states that there is currently no suitable treatment method and that participation in clinical trials is recommended.
This study evaluates targeted BCMA autologous CART cell injection in participants with relapsed/refractory light chain amyloidosis. The main purpose is to evaluate safety, preliminarily verify efficacy, and explore in vivo pharmacokinetics, pharmacodynamics, immunogenicity and related characteristics after infusion.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
The participant must personally sign an ethics-committee-approved informed consent form before study start.
Age ≥18 years.
Pathologically confirmed light chain amyloidosis.
Relapsed/refractory light chain amyloidosis previously treated with 2 or more lines of therapy.
Disqualifiers
Prior gene therapy before enrollment.
Live vaccine injection within 4 weeks before enrollment.
Other interventional clinical study drug treatment within 12 weeks before leukapheresis.
Central nervous system involvement or complete intestinal obstruction.
Trial design
Design model
Single group
Treatments tested in this trial
Targeted BCMA Autologous CART Cell Injection
Biological/VaccineAnti-BCMA chimeric antigen receptor autologous T cells are a BCMA-targeted, gene-modified autologous T-cell (CAR-T cell) immunotherapy derived from the participant's autologous peripheral blood mononuclear cells (PBMCs). The cells are transduced with lentivirus generated using a four-plasmid viral packaging system, with the pCDH-BCMA CAR plasmid as the expression vector. The product is administered as an injection by a single intravenous infusion at a dose of 1.0×10\^6 CAR-T cells/kg.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Autologous BCMA-targeted CAR-T Cell InjectionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest
The number and percentage of participants with adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) will be summarized. AEs and SAEs will be summarized by system organ class (SOC), preferred term (PT), severity, seriousness, relationship to study treatment, and outcome. AESIs include Grade 3 or higher hematologic toxicity lasting more than 30 days, excluding lymphocytopenia; hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS); Grade 3 or higher infections; uncontrolled CAR-T cell expansion; Grade 3 or higher cytokine release syndrome (CRS); Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS); progressive multifocal leukoencephalopathy; secondary malignancies; and detection of replication-competent lentivirus (RCL). AEs other than CRS and ICANS will be graded per NCI-CTCAE Version 5.0; CRS and ICANS will be graded per 2019 ASTCT criteria.
Time frame
From signing of the informed consent form through withdrawal from the study or 2 years after BCMA-targeted autologous CAR-T cell infusion, whichever occurs first.Secondary outcomes
1
Objective response rate (ORR)
Proportion of participants whose best efficacy evaluation within 6 months after infusion of BCMA-targeted Autologous CAR-T Cell Injection is partial response (PR) or complete response (CR), according to the National Comprehensive Cancer Network (NCCN) 2023 guideline and evaluation criteria for systemic light-chain amyloidosis.
Time frame
Within 6 months after infusion.2
Duration of response (DoR)
Time from the first efficacy evaluation of complete response (CR) or partial response (PR) to the first efficacy evaluation of progressive disease (PD)/relapse or death due to the study disease.
Time frame
From the first efficacy evaluation of CR/PR until the first efficacy evaluation of PD/relapse or death due to the study disease, assessed until exit from main follow-up or completion of the Day 720 visit.3
Time to response (TTR)
Time from infusion of BCMA-targeted Autologous CAR-T Cell Injection to the first efficacy evaluation of partial response (PR) or complete response (CR).
Time frame
From infusion until the first efficacy evaluation of PR or CR, assessed until exit from main follow-up or completion of the Day 720 visit.4
Progression-free survival (PFS)
Time from infusion of BCMA-targeted Autologous CAR-T Cell Injection to the first efficacy evaluation showing disease progression/relapse or death from any cause.
Time frame
From infusion until the first disease progression/relapse or death from any cause, assessed until exit from main follow-up or completion of the Day 720 visit.Sponsors and contacts
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Source ClinicalTrials.gov