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.
This is an open-label, fixed-dose exploratory clinical study to observe the safety and efficacy of targeted BCMA autologous CART cell injection in participants with relapsed/refractory light chain amyloidosis. The study is expected to enroll 30 participants and uses a fixed dose of 1.0×10\^6 CAR-T/kg. The safety observation period is 28 days after CAR-T administration. The study process includes screening, PBMC leukapheresis, pre-lymphodepletion examination, lymphodepleting conditioning, infusion of targeted BCMA autologous CART cell injection with the infusion day defined as Day 0, and the main follow-up period. Before infusion, participants receive fludarabine plus cyclophosphamide lymphodepleting conditioning from Day -5 to Day -3 for three consecutive days. The recommended regimen is cyclophosphamide 250 mg/m²/day by intravenous infusion once daily for three days and fludarabine 25 mg/m²/day by intravenous infusion once daily for three days. The investigator may adjust the conditioning regimen according to renal function and creatinine clearance, such as replacing fludarabine with bendamustine or reducing the dose. The targeted BCMA autologous CART cell injection is infused once on Day 0 by intravenous injection and completed within 30 minutes. If an adverse event occurs after conditioning and before infusion and the investigator determines that infusion should be suspended, infusion may be delayed until the adverse event recovers to a state allowing infusion. Before infusion, the investigator should reassess whether repeated lymphodepleting conditioning is needed. The main follow-up period lasts from infusion of targeted BCMA autologous CART cell injection until the participant meets the criteria for exit from main follow-up or completes the 2-year main follow-up visit at Day 720. Efficacy assessments are performed at Day 28, Day 60 and Day 90, and then every 90 days until the end of main follow-up. Participants who complete the 2-year main follow-up enter long-term follow-up. Participants who meet criteria to exit main follow-up enter long-term visits until death, withdrawal from the study, or 15 years after cell infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Anti-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.
Beijing GoBroad Boren Hospital
Beijing, Fengtai District, China
RECRUITINGNumber 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.
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.
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.
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.
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.
Overall survival (OS)
Time from infusion of BCMA-targeted Autologous CAR-T Cell Injection to death from any cause.
Time frame: From infusion until death from any cause, assessed until exit from main follow-up or completion of the Day 720 visit.
Changes in peripheral blood viral vector copy number (VCN) levels
Peripheral blood BCMA-CAR viral vector copy number (VCN) is quantitatively detected by PCR.
Time frame: Day -12 to -5 before infusion (no later than 1 minute before lymphodepletion); Days 1 and 4 (±8 h), Days 7 and 10 (±1 d), Days 14 and 21 (±2 d), Day 28 (±3 d), Days 60 and 90 and every 90 days thereafter (±14 d) through Day 720.
Changes in peripheral blood CAR-T cell concentration levels
Peripheral blood BCMA-positive CAR-T cells are detected by flow cytometry.
Time frame: Day -12 to -5 before infusion (no later than 1 minute before lymphodepletion); Days 1 and 4 (±8 h), Days 7 and 10 (±1 d), Days 14 and 21 (±2 d), Day 28 (±3 d), Days 60 and 90 and every 90 days thereafter (±14 d) through Day 720.
Maximum concentration (Cmax)
Maximum concentration of peripheral blood BCMA-CAR VCN and BCMA-positive CAR-T cells after infusion of BCMA-targeted Autologous CAR-T Cell Injection.
Time frame: Calculated from PK assessments conducted from pre-infusion sampling through the last PK assessment during main follow-up, up to Day 720 after infusion.
Time to maximum concentration (Tmax)
Time to reach the maximum concentration of peripheral blood BCMA-CAR VCN and BCMA-positive CAR-T cells after infusion of BCMA-targeted Autologous CAR-T Cell Injection.
Time frame: Calculated from PK assessments conducted from pre-infusion sampling through the last PK assessment during main follow-up, up to Day 720 after infusion.
Area under the curve from Day 0 to Day 28 (AUC0-28d)
Area under the concentration-time curve of peripheral blood BCMA-CAR VCN and BCMA-positive CAR-T cells from Day 0 to Day 28 after infusion.
Time frame: From Day 0 through Day 28 after infusion.
Area under the curve from Day 0 to Day 90 (AUC0-90d)
Area under the concentration-time curve of peripheral blood BCMA-CAR VCN and BCMA-positive CAR-T cells from Day 0 to Day 90 after infusion.
Time frame: From Day 0 through Day 90 after infusion.
Area under the curve from Day 0 to the last PK assessment (AUC0-last)
Area under the concentration-time curve of peripheral blood BCMA-CAR VCN and BCMA-positive CAR-T cells from Day 0 to the last PK assessment time point.
Time frame: From Day 0 through the last PK assessment during main follow-up, up to Day 720 after infusion.
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