This study is a single-center, open-label, dose-escalation study to observe the safety and efficacy of different doses of CAR-GPRC5D in patients with R/R MM or Plasma Cell Leukemia.
Apheresis will be performed to manufacture CAR-GPRC5D CAR-T cells. Bridging therapy is allowed between apheresis and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. Then, subjects will receive a single dose infusion of CAR-GPRC5D at 1.0, 2.0, or 3.0 x 10\^6 CAR-T cells/Kg. Subjects will be followed in the study for a minimum of 2 years after infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
CAR-GPRC5D (RD118) is an individualized, gene-modified autologous T-cell immunotherapy product targeting GPRC5D that identifies and eliminates malignant and normal cells expressing GPRC5D. The CAR structure comprises a fully human single-domain antibody fragment (VHH) targeting GPRC5D, fused with intracellular co-stimulatory (4-1BB) and activation (CD3ζ) signaling domains.
Ruijin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine
Shanghai, China
RECRUITINGIncidence of dose-limiting toxicity (DLT) by dose group
Dose limiting toxicity will be assessed after infusion in each dose group
Time frame: 28 days after CAR-T cell infusion
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity
Time frame: 2 years after CAR-T cell infusion
Objective response rate (ORR)
The percentage of participants who achieved PR or better response.
Time frame: 2 years after CAR-T cell infusion
Overall survival (OS)
OS is measured from the date of the initial infusion of CAR-GPRC5D to the date of the participant's death
Time frame: 2 years after CAR-T cell infusion
Duration of response (DOR) after administration
DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria
Time frame: 2 years after CAR-T cell infusion
Progression-free survival (PFS)
PFS is measured from the date of the initial infusion of CAR-GPRC5D of participants to the first time of disease progression or death for any reason
Time frame: 2 years after CAR-T cell infusion
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time to response (TTR)
The time interval between the first treatment of CAR-GPRC5D and the time of first recording of sCR or CR or VGPR or PR of the participants
Time frame: 2 years after CAR-T cell infusion
Time to complete Response (TTCR)
Time from CAR-GPRC5D infusion to first documentation of complete response of the participants
Time frame: 2 years after CAR-T cell infusion
Percentage of Participants With Negative Minimal Residual Disease (MRD)
MRD negative rate is defined as the proportion of participants who achieve MRD negative status by the respective time point
Time frame: 2 years after CAR-T cell infusion
Pharmacokinetics - Cmax
The maximum transgene level at Tmax
Time frame: 2 years after CAR-T cell infusion
Pharmacokinetics - Tmax
Time to peak transgene level
Time frame: 2 years after CAR-T cell infusion
Pharmacokinetics - AUC0-28days
Area under the curve of CAR-T cells from time zero to Day 28
Time frame: 2 years after CAR-T cell infusion
Pharmacokinetics - AUC0-90days
Area under the curve of CAR T cells from time zero to Day 90
Time frame: 2 years after CAR-T cell infusion
PD endpoints - the level of free CAR-GPRC5D
The content of free CAR-GPRC5D in peripheral blood will be detected at each time point
Time frame: 2 years after CAR-T cell infusion
PD endpoints - the levels of CAR-T-related serum cytokines
The concentration levels of CAR-T-related serum cytokines (such as IL-6) will be detected at each time point
Time frame: 2 years after CAR-T cell infusion
Health-related quality of life assessment
HRQoL will be assessed by the European Organization for Cancer Research and Treatment Quality of Life Questionnaire (EORTC-QLQ-C30)
Time frame: 2 years after CAR-T cell infusion
Evaluation of lymphocyte subsets
Lymphocyte subsets will be assessed by FACS
Time frame: 2 years after CAR-T cell infusion
Levels of immunoglobulins
Immunoglobulins in peripheral blood will be assessed to monitor changes
Time frame: 2 years after CAR-T cell infusion