This study is a multi-center, single-arm clinical study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamic characteristics of CT103A as the first-line treatment in newly diagnosed high-risk multiple myeloma subjects with induction chemotherapy as bridging therapy.
Before enrollment, subjects will receive chemotherapy regimen of either Bortezomib-Lenalidomide-Dexamethasone (VRD), Bortezomib-Cyclophosphamide-Dexamethasone (PCD) or Bortezomib-Adriamycin-Dexamethasone (PAD) as induction therapy for 3 cycles. Evaluation will be made after 2 cycles of chemotherapy. If the subject is not intended to have stem cell transplantation or unsuitable for autologous hematopoietic stem cell transplantation (ASCT) as judged by the investigator, he/she will receive the 3rd cycle of chemotherapy. If the subject meets the inclusion criteria, he/she will be enrolled in the study. Peripheral blood mononuclear cell (PBMC) will be collected to manufacture CT103A. After PBMC collection, the subject will receive another cycle of chemotherapy and evaluated. Lymphodepletion with fludarabine and cyclophosphamide will be performed for three consecutive days. After 1-day rest, subjects will receive a single infusion of CT103A at 1.0 ×10\^6 /kg. Subjects will be followed in the study for a minimum of 2 years after CT103A infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after CT103A infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
CT103A is a customized, BCMA-targeted genetically modified autologous T cell immunotherapy, which can identify and eliminate malignant and normal cells expressing BCMA. CAR specifically recognizes BCMA with single chain fragment variable (ScFv), and promotes the activation, proliferation, cytokine secretion and target cell killing of CAR-T through the CD3ζ domain. And 4-1BB enhances the expansion and persistence of CT103A. CT103A will be infused at 1.0×10\^6 /kg via intravenous drip within 24h to 72h after chemotherapy conditioning regimen at the recommended infusion rate of 3-5 mL/min.
Anhui Provincial Cancer Hospital
Hefei, Anhui, China
The First People's Hospital of Changzhou
Changzhou, Jiangsu, China
Jiangsu Province Hospital
Nanjing, Jiangsu, China
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, China
Proportion of Minimal Residual Disease (MRD)-negative subjects
The proportion of subjects who achieve MRD-negativity after CT103A infusion.
Time frame: Up to 2 years after CT103A infusion
Median progression-free survival (mPFS)
The median time from the date of CT103A infusion to the date of first disease progression or death from any cause.
Time frame: Up to 2 years after CT103A infusion
Best overall response (BOR)
The proportion of subjects who achieve stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) after CT103A infusion.
Time frame: Up to 2 years after CT103A infusion
Median survival (mOS)
The median time from the date of CT103A infusion to the date of death from any reason.
Time frame: Up to 2 years after CT103A infusion
Event-free survival (EFS)
The time from date of CT103A infusion to the date of death from any reason, relapse, treatment failure, disease progression or initiation of other anti-tumor treatment, whichever comes first;
Time frame: Up to 2 years after CT103A infusion
Duration of response (DOR)
The time from the first assessment of sCR or CR or VGPR or PR to the first assessment of disease progression or death from any cause;
Time frame: Up to 2 years after CT103A infusion
Safety endpoint
Incidence of treatment-emergent adverse events (TEAE) and Treatment-related adverse events (TRAE).
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Time frame: Up to 2 years after CT103A infusion
Pharmacokinetic(PK) endpoint
The maximum CT103A concentration and the copy number of the lentiviral vector (vector copy number, VCN) in peripheral blood (Cmax)
Time frame: Up to 90 days after CT103A infusion
PK endpoint - Tmax
The time to reach the maximum concentration (Tmax)
Time frame: Up to 90 days after CT103A infusion
PK endpoint - AUC 0 to 28d and AUC 0 to 90d
The area under the concentration time curve from time zero to day 28 (AUC0-28d) and from time zero to day 90 (AUC0-90d)
Time frame: Up to 90 days after CT103A infusion
Levels of Soluable BCMA
The levels of soluble BCMA in peripheral blood at each time point.
Time frame: Up to 90 days after CT103A infusion
PD endpoint
The levels of cytokines (IL-6, serum ferritin, etc.) in peripheral blood at each time point
Time frame: Up to 90 days after CT103A infusion