This is an open-label, single-arm, Phase 2 study to evaluate the efficacy and safety of IL-15-armored chimeric antigen receptor T-cell (CAR-T) therapy in subjects with relapsed or refractory multiple myeloma and plasma cell leukemia.
This is an open-label, single-arm, Phase 2 study to evaluate the efficacy and safety of IL-15-armored CAR-T therapy in subjects with relapsed or refractory (R/R) multiple myeloma (MM) and plasma cell leukemia (PCL). Subjects with persistent measurable residual disease (MRD) positivity or conversion from MRD-negative to MRD-positive status are also eligible. IL-15-armored CAR-T cells are autologous T lymphocytes genetically engineered to express a chimeric antigen receptor along with IL-15. The co-expression of IL-15 is intended to enhance in vivo expansion, persistence, and anti-tumor activity. Subjects will undergo leukapheresis for CAR-T cell manufacturing, followed by lymphodepletion prior to infusion. Bridging therapy is permitted at the investigator's discretion, and radiotherapy is allowed before infusion for subjects with extramedullary disease. After infusion, the efficacy and safety will be evaluated by the investigators. Exploratory Objectives and Correlative Studies: In addition to the primary efficacy and safety evaluations, exploratory analyses will be conducted to investigate clinical, biological, and treatment-related factors associated with treatment response and severe toxicity, with the aim of developing predictive models. Multi-omics approaches, including single-cell sequencing, bulk RNA sequencing, and spatial transcriptomics, will be employed to characterize the dynamics of the tumor microenvironment. Circulating tumor DNA (ctDNA) will be longitudinally collected from baseline through post-infusion follow-up. The associations between ctDNA dynamics and clinical outcomes will be assessed. The clinical efficacy and biological mechanisms of radiotherapy (including site-directed radiotherapy and low-dose intestinal irradiation) in combination with CAR-T cell therapy will also be explored.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
BCMA-targeted: 1.0/1.5/2.0 × 10\^6 CAR-T cells; CD19/BCMA dual-targeted: 1.0/1.5/2.0 × 10\^6 CAR-T cells; GPRC5D-targeted: 1.0/2.0/3.0 × 10\^6 CAR-T cells.
The First Hospital of Jilin University
Changchun, Jilin, China
RECRUITINGOverall response rate (ORR)
Percentage of participants with presence of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). ORR assessment will be based on International Myeloma Working Group (IMWG) response criteria.
Time frame: From infusion to 12 months
Complete Response Rate
Percentage of participants who achieved CR or sCR according to IMWG Uniform Response Criteria for Multiple Myeloma
Time frame: From infusion to 12 months
MRD-negative rate
Achieving measurable residual disease (MRD) negativity, as determined by multiparameter flow cytometry (MFC) or next-generation sequencing (NGS) after CAR-T cells infusion.
Time frame: From infusion to 12 months
CR/MRD-negative rate
Percentage of participants who achieved both CR and MRD negativity with a sensitivity of 10\^-4 or better within 12 months post infusion.
Time frame: From infusion to 12 months
Time to Response
Time from infusion to first documentation of response of PR or better.
Time frame: From infusion to 12 months
Duration of Response (DOR)
Time from first documentation of PR or better to first documentation of disease progression or death from any cause, whichever occurs first.
Time frame: From first documentation of response through the end of follow-up (up to 24 months)
Progression-free survival (PFS)
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Time from first infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first.
Time frame: From infusion through the end of follow-up (up to 24 months)
Overall Survival (OS)
Time from first infusion to time of death due to any cause.
Time frame: From infusion through the end of follow-up (up to 24 months)
Cmax
The maximum transgene level at Tmax.
Time frame: From infusion to 12 months
Tmax
The time of maximum observed transgene level, obtained directly from the observed transgene level-time.
Time frame: From infusion to 12 months
AUC (0-180 days)
The area under the curve (AUC) of the transgene level from the time of dosing to Day 180.
Time frame: at Day 180 post infusion
Number of Participants With Safety Related Events
Number of participants with adverse events (AEs), adverse events of special interest (AESI), serious adverse events (SAEs), cytokine release syndrome, neurotoxicity, infection, and clinically significant laboratory abnormalities.
Time frame: From enrollment through the end of follow-up (up to 24 months)