This study is a single-armed, open-label, multicenter Phase 1/2 study to evaluate the efficacy and safety of Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (Equecabtagene Autoleucel) in subjects with relapsed and refractory Multiple Myeloma.
This study is divided into two stages: Part 1 and Part 2. Part 1: For exploratory research purposes, no more than 3 subjects will be enrolled at an exploratory dose. Part 2: The purpose of this phase is to explore the efficacy of Equecabtagene Autoleucel (Eque-cel) as a last-line treatment for RRMM and further confirm its safety. In this Study,Leukapheresis procedure will be performed to manufacture Eque-cel modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide is performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of Eque-cel at 1.0 x 10\^6 CAR+ T cells/Kg or 0.5 x 10\^6 CAR+ T cells/Kg(if all three subjects in Part 1 experience the Toxicity Requiring Dose Reduction). Subjects will be followed in the study for a minimum of 2 years after Eque-cel infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Eque-cel consists of autologous T lymphocytes transduced with anti-BCMA CAR lentiviral vector that contains a unique CAR structure with a fully human single-chain variable fragment (scFv).
Institute of Science Tokyo Hospital
Bunkyo-ku, Tokyo, Japan
Nihon University Itabashi Hospital
Itabashi-ku, Tokyo, Japan
Japanese Red Cross Medical Center
Shibuya-ku, Tokyo, Japan
Safety endpoint (Part 1)- Adverse Event(AEs)
Incidence and severity of adverse events as assessed by NCI-CTCAE v5.0 (except CRS and ICANS assessed according to the criteria of 2019 ASTCT criteria).
Time frame: up to 2 years from Eque-cel infusion
Safety endpoint (Part 1)-CRS
Incidence and severity of cytokine release syndrome (CRS; based on the 2019 ASTCT criteria)
Time frame: up to 2 years from Eque-cel infusion
Safety endpoint (Part 1)-ICANS
Incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS).( based on the 2019 ASTCT criteria)
Time frame: up to 2 years from Eque-cel infusion
Efficacy endpoint (Part 2): Independent Review Committee (IRC)-assessed ORR
Rate of best response (PR, very good PR, CR, sCR) after Eque-cel infusion in all subjects at the time the last subject completed the 6-month follow-up.
Time frame: up to 2 years from Eque-cel infusion
Safety endpoint (Part 2)- Adverse Event(AEs)
Incidence and severity of adverse events as assessed by NCI-CTCAE v5.0 (except CRS and ICANS assessed according to 2019 ASTCT criteria).
Time frame: up to 2 years from Eque-cel infusion
Efficacy endpoint -Investigator-assessed overall response rate (ORR)
Rate of best response (PR, very good PR, CR, sCR) after Eque-cel infusion for all subjects at the time the last subject completed the 6-month follow-up.
Time frame: up to 2 years from Eque-cel infusion
Efficacy endpoint -IRC- and investigator-assessed ORR
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Rate of best response (PR, VGPR, CR, sCR) within 1 month, 3 months, and 6 months after Eque-cel infusion.
Time frame: up to 2 years from Eque-cel infusion
Efficacy endpoint -IRC and investigator-assessed duration of response (DOR)
The period from the first response (PR, VGPR, CR, sCR) to the date of the first documented evidence of disease progression or death from any cause, as defined by the IMWG criteria after treatment.
Time frame: up to 2 years from Eque-cel infusion
IRC and investigator-assessed time to response (TTR)
The period from Eque-cel infusion to the date of the first documented response (PR or better).
Time frame: up to 2 years from Eque-cel infusion
IRC and investigator-assessed time to complete response (TTCR)
The period from Eque-cel infusion to the date of complete response (CR) or stringent complete response (sCR).
Time frame: up to 2 years from Eque-cel infusion
Minimal residual disease (MRD) assessment by flow cytometry
The proportion of subjects achieving MRD negativity and the duration of MRD negativity.
Time frame: up to 2 years from Eque-cel infusion
IRC and investigator-assessed progression-free survival (PFS)
The period from Eque-cel infusion to the date of first disease progression or death from any cause.
Time frame: up to 2 years from Eque-cel infusion
Overall survival (OS)
The period from Eque-cel infusion to death from any cause.
Time frame: up to 2 years from Eque-cel infusion
Pharmacokinetic Endpoint-Cmax
The maximum concentration (Cmax) of BCMA CAR-T cells in peripheral blood after Eque-cel infusion.
Time frame: up to 2 years from Eque-cel infusion
Pharmacokinetic Endpoint-Tmax
The time for BCMA CAR-T cells to reach the maximum concentration (Tmax) after Eque-cel infusion.
Time frame: up to 2 years from Eque-cel infusion
Pharmacokinetic Endpoint-AUC
Area under the curve of 28, 90 days and the last time point of PK measurement (AUC0-28d, AUC0-90d, AUC0-last) for BCMA CAR-T cells.
Time frame: up to 2 years from Eque-cel infusion
Pharmacokinetic Endpoint-Cmax
The maximum concentration (Cmax) of lentiviral vector copy number (VCN) in peripheral blood after Eque-cel infusion.
Time frame: up to 2 years from Eque-cel infusion
Pharmacokinetic Endpoint-Tmax
The time for lentiviral vector copy number (VCN) to reach the maximum concentration (Tmax) after Eque-cel infusion.
Time frame: up to 2 years from Eque-cel infusion
- Pharmacokinetic Endpoint-AUC
Area under the curve of 28, 90 days and the last time point of PK measurement (AUC0-28d, AUC0-90d, AUC0-last) for lentiviral vector copy number (VCN).
Time frame: up to 2 years from Eque-cel infusion
Pharmacodynamic Endpoint-sBCMA
The concentration of soluble BCMA in peripheral blood .
Time frame: up to 2 years from Eque-cel infusion
Pharmacodynamic Endpoint-C-reactive protein (CRP)
Changes in the levels of CRP.
Time frame: up to 2 years from Eque-cel infusion
Pharmacodynamic Endpoint -Ferritin
Changes in the levels of Ferritin.
Time frame: up to 2 years from Eque-cel infusion
Pharmacodynamic Endpoint -Interleukin-6 (IL-6)
Changes in the levels of IL-6.
Time frame: up to 2 years from Eque-cel infusion