Allogeneic UCB-derived, Dual-targeting BCMA/CD19 CAR-T for Relapsed/Refractory Multiple Myeloma

NCT07139509 | Recruiting Phase 1 DMC

• 1 other identifier: UC-MM-2024-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 2.Which dose level is the optimal biological dose (OBD)?
3. 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?
4. 4.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).
5. 5.rest for 2 days on Day-2 and Day-1. Tumor burden should be re-evaluated and chemotherapy side effects assessment.
6. 6.receive allogeneic cord blood-derived CAR-T cells infusion
7. 7.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.

Conditions

Relapsed/Refractory Multiple Myeloma(MM)

Keywords

allogeneic CAR-T; umbilical cord blood-derived; relapsed/refractory multiple myeloma

Outcome Measures

Primary Outcomes (2)

• the 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.

  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

  within 28 days after UCAR-T infusion

Secondary Outcomes (5)

• Overall response rate (ORR) of Multiple Myeloma (MM)

  from the UCAR-T infusion to death from any cause (censored), up to 2 years.

• Overall survival (OS) of MM

  up to 2 years after UCAR-T cells infusion

• Progression-free survival (PFS) of MM

  up to 2 years after UCAR-T cells infusion

• Duration of Response (DOR) of MM

  up to 2 years after UCAR-T cells infusion

• Quality of Life (QoL)

  at Baseline, Month 1, 3, 6, 9,12, 18 and 24.

Study Arms (1)

UCAR-T cells treatment

EXPERIMENTAL

Drug: allogeneic cord blood-derived, dual-targeting CD19/BCMA CAR-T cells

Interventions

allogeneic cord blood-derived, dual-targeting CD19/BCMA CAR-T cells DRUG

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.

UCAR-T cells treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years (inclusive of boundary values), with no limitation on gender;
• Diagnosed with multiple myeloma in accordance with the "Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China (2022 Revision)" :
• Bone marrow monoclonal plasma cell percentage ≥10% and/or histopathological evidence of plasmacytoma; and presence of at least one of the following SLiM CRAB features:
• SLiM refers to:
• S: Bone marrow monoclonal plasma cell percentage ≥60%;
• Li: Ratio of involved to uninvolved serum free light chain ≥100 (with the involved light chain value being at least ≥100 mg/L);
• M: MRI detection of \>1 focal bone lesion larger than 5 mm.
• CRAB refers to:
• C: Corrected serum calcium \>2.75 mmol/L \[Corrected serum calcium (mmol/L) = serum total calcium (mmol/L) - 0.025×serum albumin concentration (g/L) + 1.0 (mmol/L), or corrected serum calcium (mg/dl) = serum total calcium (mg/dl) - serum albumin concentration (g/L) + 4.0 (mg/dl)\];
• R: Renal insufficiency (creatinine clearance \<40 ml/min or serum creatinine \>177 μmol/L);
• A: Anemia (hemoglobin \< lower limit of normal by 20 g/L or \<100 g/L);
• B: Lytic bone lesions, demonstrated by radiographic imaging (X-ray, CT, MRI, or PET-CT) showing one or more lytic bone lesions.
• Definition of relapsed/refractory multiple myeloma:
• Must have received at least three therapeutic regimens (The induction and maintenance therapies associated with hematopoietic stem cell transplantation, whether one or both were performed, are considered as one therapeutic regimen);
• Must have been treated with a proteasome inhibitor, an immunomodulatory agent, or an anti-CD38 antibody;

You may not qualify if:

• Participants meeting any of the following criteria are not eligible for enrollment in this study:
• Lactating women;
• Unwillingness to undergo follow-up for 15 years;
• Poor compliance with the study procedures;
• Individuals under legal guardianship or conservatorship;
• with a history of ≥Grade 4 CRS or neurotoxicity in previous CAR-T therapy ;
• Within 5 half-lives of prior anti-MM therapies (including approved therapies and other investigational drugs) before enrollment;
• Disease progression after debulking therapy;
• Active central nervous system (CNS) abnormalities or history of irreversible severe CNS toxicity from prior MM treatment leading to CNS organic lesions or CNS dysfunction;
• Radioimmunotherapy or radiotherapy within 8 weeks before enrollment;
• Hematopoietic stem cell transplantation (HSCT) within 3 months before screening, donor lymphocyte infusion within 6 weeks before screening; patients who have undergone autologous stem cell transplantation within 100 days; patients who have undergone solid organ transplantation;
• Active acute or chronic graft-versus-host disease (GvHD) requiring systemic therapy within 4 weeks before UC503 cells infusion;
• Patients with autoimmune diseases who are unable to discontinue systemic immunosuppressive therapy;
• Patients currently receiving or having received high-dose (total dose of 60 mg dexamethasone or equivalent other corticosteroid) systemic corticosteroid therapy within 4 weeks before lymphodepletion;
• Known hypersensitivity to UCAR-T or any of its components;

Sponsors & Collaborators

• Xi'an No.3 Hospital: lead
• Ucello Therapeutics Co., Limited: collaborator

Study Sites (1)

Xi'an No.3 Hospital

Xi’an, Shanxi, 710016, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Xiequn Chen, M.D.

  Xi'an No.3 Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiequn Chen, M.D.

CONTACT

+86 29 6130 6285; cxq@nwu.edu.cn

Qiang Zou, Ph.D. & M.D.

CONTACT

86-18908237461; zouqiang@ucellotx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hematology & Principal Investigator

Study Record Dates

• First Submitted: July 20, 2025
• First Posted: August 24, 2025
• Study Start: October 3, 2024
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: November 25, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months and ending 2 years after the publication of results

Locations

CN (1)