A Phase Ⅱ Clinical Study Evaluating the Efficacy and Safety of Human BCMA Targeted T Cells Injection(BCMA CAR-T) Therapy for R/R MM. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of BCMA CAR+ T cells.
Participants with relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, Computedtomography (CT)/Magnetic Resonance Imaging(MRI)/Positron Emission Tomography(PET), and blood draws. Participants receive chemotherapy prior to the infusion of BCMA CAR+ T cells. After the infusion, participants will be followed for side effects and effect of BCMA CAR+ T cells. Study procedures may be performed while hospitalized.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
A single dose of predetermined level CAR-positive T cells will be infused.
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGThe First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, China
RECRUITINGObjective Response Rate (ORR) at 3 months post infusion as evaluated by the Independent Review Committee
ORR at 3 months post infusion as evaluated by the Independent Review Committee (IRC) includes stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR).
Time frame: 3 months post infusion
Duration of remission (DOR) after administration
DOR refers to the time from the first assessment of the tumor for complete response and above efficacy to the first assessment of disease progression or death of any cause;
Time frame: 2~3 years post infusion
Progression-free Survival (PFS) after administration
PFS refers to the time from the start of cell infusion to the first assessment of tumor progression or death from any cause;
Time frame: 2~3 years post infusion
Overall Survival (OS) after administration
OS refers to the time from cell infusion to death due to any cause;
Time frame: 2~3 years post infusion
Objective Response Rate (ORR) at 3 months post infusion as evaluated by the Investigator
ORR at 3 months post infusion as evaluated by the Investigator;
Time frame: 3 months post infusion
Objective Response Rate (ORR) at 6 months post infusion as evaluated by the Independent Review Committee
ORR at 6 months post infusion as evaluated by the Independent Review Committee (IRC);
Time frame: 6 months post infusion
Percentage of Subjects With Negative Minimal Residual Disease (MRD)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
MRD negative rate is defined as the proportion of subjects who achieve MRD negative status;
Time frame: 2~3 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 International Myeloma Working Group(IMWG) criteria (2016);
Time frame: 2~3 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: 2~3 years post infusion
Change from Baseline in Perform Status as Measured by Eastern Cooperative Oncology Group(ECOG)Score(0-2)
Eastern Cooperative Oncology Group(ECOG) Performance Status Score(0-2) will be assessed by the inverstigator at baseline and the respective time point, higher scores mean a worse performance status.
Time frame: 2~3 years post infusion
The occurrence rate of adverse events grade ≥ 3 assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Safety Indicators
Time frame: 2~3 years post infusion
Change in body weight over time after reinfusion
Safety Indicators
Time frame: 2~3 years post infusion
Pharmacokinetic indicators:Maximum CAR level inperipheral blood or bone marrow (Cmax)
The highest concentration of Human BCMA Targeted T Cells Injection amplified in peripheral blood or bone marrow after infusion (Cmax) ;
Time frame: 2~3 years post infusion
Pharmacokinetic indicators: Time to peak CAR level in blood or bone marrow (Tmax)
The time to reach the highest concentration of Human BCMA Targeted T Cells Injection in peripheral blood or bone marrow after infusion (Tmax) ;
Time frame: 2~3 years post infusion
Pharmacokinetic indicators: 28-day Area under the curve of the CAR level in blood or bone marrow (AUC0-28d)
The 28-day area under the curve of Human BCMA Targeted T Cells Injection in peripheral blood or bone marrow after infusion(AUC0-28d);
Time frame: 2~3 years post infusion
Pharmacodynamic indicators: the concentration level of soluble BCMA (sBCMA) in peripheral blood
The concentration level of soluble BCMA (sBCMA) in peripheral blood at various time points after infusion of Human BCMA Targeted T Cells Injection;
Time frame: 2~3 years post infusion
Pharmacodynamic indicators: the concentration level of CAR-T cell-related serum cytokines such as C-Reactive Protein(CRP) in peripheral blood;
Effectiveness Metrics
Time frame: 2~3 years post infusion
Pharmacodynamic indicators: the concentration level of CAR-T cell-related serum cytokines such as Interleukin-6(IL-6), IL-2, IL-10, Tumor Necrosis Factor (TNF-α),Interferon-γ(IFN-γ)in peripheral blood;
Effectiveness Metrics
Time frame: 2~3 years post infusion
Immunogenicity: Anti-drug antibody(ADA) positive ratio
Immunogenicity study evaluated the immune responses to anti-BCMA scFV including the detection of anti-scFV antibodies;
Time frame: 2~3 years post infusion
Immunogenicity: Neutralizing Antibody(Nab) positive ratio
Immunogenicity study evaluated the immune responses to anti-BCMA scFV including the detection of neutralizing antibodies (NAbs) against scFV.
Time frame: 2~3 years post infusion