The purpose of this clinical trial is to learn if allogeneic cord blood-derived CAR-T cell drug works to treat Multiple Myeloma (MM) including Bone-related extramedullary (EMB) disease and extramedullary extraosseous disease(EME) in adults. It will also learn about the safety of the allogeneic cord blood-derived CAR-T cell drug. The main questions it aims to answer are: 1. What adverse events occur and the incidence rate of DLTs within 28 days and UCAR-T-related AEs within 28 days after the allogeneic cord blood-derived CAR-T cell injection for multiple myeloma (MM)? 2. Which dose level is the optimal biological dose (OBD)? 3. What is the overall responserate (ORR), including stringent complete response (sCR), completeresponse (CR),very good partial response (VGPR), partial response (PR), minimal Response (MR) and DOR, PFS, RFS, OS? Participants will: 1. be pretreated with FC regimen, fludarabine (30mg/m²/d, days -5, -4, and -3) and cyclophosphamide (300\~500 mg/m²/d, day -5,-4, and -3). 2. rest for 2 days on Day-2 and Day-1. Tumor burden should be re-evaluated and chemotherapy side effects assessment. 3. receive allogeneic cord blood-derived CAR-T cells infusion 4. Visit the clinic at D28, 1 month, 2 months, 3 months, 4 months, 6 months, 9 months and 1 year after CAR-T cells infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
dosage form: UCAR-T cell injection Route of Administration: Single intravenous injection Participants will receive lymphodepletion with fludarabine (30 mg/m²/day) and cyclophosphamide (500 mg/m²/day) from Day -5 to -3, prior to UCAR-T cell infusion on Day 0.
Xi'an No.3 Hospital
Xi’an, Shanxi, China
RECRUITINGthe incidence rate of UCAR-T-related adverse events
Incidence of adverse events(AEs) after infusion, The number, frequency, severity, and laboratory findings of all treatment-related adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form., Up to 28 days after infusion. UCAR-T therapy-Related Adverse Events will be Assessed by CTCAE v4.0.
Time frame: from lymphodepletion (D-6) through day 28 post-infusion (D+28).
The incidence rate of Dose limited toxicity (DLTs)
Dose limited toxicity(DLT) was defined as the occurrence of any of the following adverse events within 28 days of the infusion of CAR-T cells after optimal supportive treatment, which were discussed with the investigator and determined to be associated or likely to be associated with the infusion. Any DTLs within 28 days after UCAR-T infusion will be recorded in time, including severity, occurrence time, duration, treatment methods and prognosis. Specific syndromes will be graded using the following dedicated criteria: 1. Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): 2018 American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading 2. Acute Graft-versus-Host Disease (aGvHD): MAGIC (Mount Sinai Acute GVHD International Consortium) Criteria 3. Tumor Lysis Syndrome (TLS): Cairo-Bishop Definition 4. Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis (IEC-HS): 2018 ASTCT Panel Guidelines
Time frame: within 28 days after UCAR-T infusion
Overall response rate (ORR) of Multiple Myeloma (MM)
Anti-multiple myeloma response will be assessed according to the International Myeloma Working Group (IMWG) Uniform Response Criteria, including: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD), Progressive Disease (PD). Overall Response Rate (ORR) =sCR+CR+VGPR+PR+MR. Assessment of ORR at month 1, 2, 3, 6, 12, 18 and 24.
Time frame: from the UCAR-T infusion to death from any cause (censored), up to 2 years.
Overall survival (OS) of MM
the time interval from the date of UCAR-T cells infusion to the date of death from any cause.
Time frame: up to 2 years after UCAR-T cells infusion
Progression-free survival (PFS) of MM
The time interval from the date of UCAR-T infusion to the date of first documented disease progression per International Myeloma Working Group (IMWG) criteria, or death from any cause, whichever occurs earlier.
Time frame: up to 2 years after UCAR-T cells infusion
Duration of Response (DOR) of MM
The time interval from the date of first documented confirmed response (≥ partial response per IMWG 2016 criteria) after UCAR-T infusion to the date of MM progression or death from any cause, whichever occurs earlier.
Time frame: up to 2 years after UCAR-T cells infusion
Quality of Life (QoL)
Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale (For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome) to measure Quality of life at Baseline, Month 1, 3, 6, 9,12, 18 and 24.
Time frame: at Baseline, Month 1, 3, 6, 9,12, 18 and 24.
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