This study is a single-arm, open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of Human Derived anti-BCMA CAR-T Injection , and to preliminarily observe the efficacy of the trial drug in patients with relapsed/refractory multiple myeloma.
Subjects withe relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility including disease assessments, a physical exam, Electrocardiograph, Computed tomography(CT)/Magnetic Resonance Imaging(MRI)/Positron Emission Tomography(PET),liver/renal function tests, complete blood count with differential and complete metabolic profile and etc.. Subjects will receive precondtioning chemotherapy prior to the infusion of BCMA CAR- T cells. After the infusion, subjects will be followed for adverse events pharmacokinetic/pharmacodynamics characteristics, efficacy, of BCMA CAR-T cells. Study procedures may be performed while hospitalized.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Autologous genetically modified anti-BCMA CAR transduced T cells
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, China
Dose limited toxicity(DLT)
Safety Indicator
Time frame: 28 days post infusion
Pharmacokinetics parameters - Maximum CAR level in blood and CAR level in bone marrow(Cmax)
Effectiveness Metrics
Time frame: 2 years post infusion
Pharmacokinetics parameters -Time to peak CAR level in blood (Tmax)
Effectiveness Metrics
Time frame: 2 years post infusion
Pharmacokinetics parameters - 28-day Area under the curve of the CAR level in blood(AUC0-28)
Effectiveness Metrics
Time frame: 2 years post infusion
Pharmacodynamics characteristics - Cytokines Concentrations,cytokines level in blood
Effectiveness Metrics
Time frame: 2 years post infusion
Pharmacodynamics characteristics -Clonal bone marrow plasma cells level
Effectiveness Metrics
Time frame: 2 years post infusion
Overall Response Rate (ORR) at 3 month post infusion
ORR defined as proportion of subjects who achieved Partial remission(PR) or better according to the International Myeloma Working Group response criteria (2016) (IMWG 2016) as determined by an Investigator assessment at 3 month post infusion.
Time frame: 3 month post infusion
Percentage of Subjects With Negative Minimal Residual Disease (MRD)
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MRD negative rate is defined as the proportion of subjects who achieve MRD negative status
Time frame: 2 years post infusion
Duration of Subjects With Negative Minimal Residual Disease (MRD)
MRD duration will calculated among MRD negative responders fom the date of initial MRD negative to the date of first documented evidence of MRD positive, as defined in the IMWG criteria (2016).
Time frame: 2 years post infusion
Number of Subjects with Adverse Events
Adverse event is any untoward medical event that occurs in a subject administered an investigational drug.
Time frame: 2 years post infusion
Change from Baseline in Perform Status as Measured by Eastern Cooperative Oncology Group(ECOG)Score(0-4)
Eastern Cooperative Oncology Group(ECOG) Performance Status Score(0-4) will be assessed by the inverstigator at baseline and the respective time point, higher scores mean a worse performance status.
Time frame: 2 years post infusion
Change from Baseline in complete blood count with differential and blood biochemical examination
complete blood count with differential and blood biochemical examination will be assessed by the investigator at the respective time point.
Time frame: 2 years post infusion
Change from Baseline in Physical Exam
physical exam will be assessed by the inverstigator at the respective time poin.
Time frame: 2 years post infusion
Progression-free Survival (PFS)
PFS defined as time from date of initial infusion of CAR-T to date of first disease progression according to IMWG criteria (2016) , or death due to any cause, whichever occurs first.
Time frame: 2 years post infusion
Overall Survival (OS)
OS is measured from the date of the initial infusion of CAR-T to the date of the subject's death.
Time frame: 2 years post infusion
Duration of Response (DOR)
DOR will be calculated among responders (with a PR or better response) from the date of initial response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria (2016).
Time frame: 2 years post infusion