Universal CAR-T Cells (REVO-UWD-00B) for Refractory and Relapsed Multiple Myeloma

NCT06663046 | Suspended Early Phase 1

• 1 other identifier: 2024-REVO-UWD-BCMA
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm, investigator-initiated clinical trial. The primary objective is to evaluate the safety and preliminary efficacy of administering universal BCMA CAR-T cells to subjects with refractory and relapsed multiple myeloma. Eligible participants will undergo FC preconditioning after signing an informed consent form, followed by a one-time injection of universal UWD-00B cells to assess its safety and efficacy. Subjects will be hospitalized for a period, and after discharge, they will undergo periodic efficacy assessments and long-term survival follow-up for at least five years.

Conditions

Multiple Myleoma; Refractory and Relapsed Multiple Myeloma

Keywords

BCMA; REVO-U platform; Off-the-shelf CAR-T therapy

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  The highest dose of UWD-19 CAR-T cells that can be administered without causing unacceptable side effects, measured during the dose escalation phase.

  Within the first month post-infusion.

• Dose-Limiting Toxicities (DLT)

  The incidence of treatment-related toxicities that prevent further dose escalation.

  Within the first month post-infusion.

• Treatment-Emergent Adverse Events (TEAE)

  The frequency and severity of adverse events that arise following the administration of UWD-00B CAR-T cells.

  From the administration of UWD-00B CAR-T cells through six months post-infusion

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Measured at 3 and 6 months after treatment

• Progression-Free Survival (PFS)

  From the start of treatment up to 5 years

• Overall Survival (OS)

  From the start of treatment up to maximum follow-up period of five years

• Duration of Response (DOR)

  From the administration of UWD-00B CAR-T cells to a maximum follow-up period of five years

Study Arms (1)

Off-the-shelf REVO-UWD-00B

EXPERIMENTAL

Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning, followed by a one-time injection of universal UWD-00B cells

Biological: Single dose injection of certain dose of UWD-00B; Drug: MMF Immunosuppression

Interventions

MMF Immunosuppression DRUG

One day after the completion of fludarabine preconditioning (D-2), initiate oral mycophenolate sodium at a dose of 1440 mg twice daily (BID) for 15 consecutive days, or extend the duration appropriately based on CAR-T cell expansion status (discontinuation may occur at the end of CAR-T cell expansion or on the day of patient discharge). The maximum duration of administration must not exceed 30 days.

Off-the-shelf REVO-UWD-00B

Single dose injection of certain dose of UWD-00B BIOLOGICAL

Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning after signing an informed consent form, followed by a one-time injection of certain dose of universal UWD-00B cells

Off-the-shelf REVO-UWD-00B

Eligibility Criteria

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

You may qualify if:

• The patient or their guardian understands and voluntarily signs the informed consent form and is expected to complete the study's follow-up assessments and treatments.
• Age between 18 and 75 years, with no gender restrictions. Diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) criteria.
• Documented evidence of relapsed/refractory or primary refractory multiple myeloma, defined as follows:
• Relapsed/Refractory: Lack of response to salvage therapy (defined as no minimal response (MR) or disease progression during treatment), or disease progression within 60 days of the last treatment, or progression after achieving MR or better.
• Primary Refractory: No response (MR or better) to any previous treatment, with no clinical progression or minimal M-protein change, or meeting criteria for primary refractory progression.
• Presence of measurable disease at screening by any of the following criteria: serum M-protein ≥ 1.0 g/dL, urine M-protein ≥ 200 mg/24 hours, or for light-chain myeloma without measurable disease in serum or urine, serum free light chain (FLC) ≥ 10 mg/dL with abnormal serum immunoglobulin κ/λ FLC ratio.
• Resolution of prior treatment-related toxicities to Grade \<2 per CTCAE (unless related to underlying malignancy or deemed stable and not impacting safety or efficacy).
• ECOG performance status 0-2 and an expected survival of more than 3 months.
• Laboratory values meeting the following standards, indicating adequate organ and marrow function, with no severe hematological or organ impairment:
• Serum albumin ≥ 25 g/L Hemoglobin ≥ 8.0 g/dL (without RBC transfusion in the prior 7 days; recombinant human erythropoietin permitted) Absolute neutrophil count ≥ 0.75×10⁹/L (growth factor support allowed if discontinued ≥7 days before test) Platelet count ≥ 60×10⁹/L (no platelet transfusion within 7 days) Creatinine clearance ≥ 30 mL/min/1.73 m² (using kidney disease formula or 24-hour urine collection) ALT and AST ≤ 3.0×ULN Total bilirubin ≤ 2.0×ULN (Gilbert's syndrome exception with direct bilirubin ≤ 1.5×ULN) PT and APTT \< 2×ULN Blood oxygen saturation ≥ 95%

You may not qualify if:

• Diagnosis or treatment of other invasive malignancies within 3 years, with the exception of curatively treated non-melanoma skin cancer or malignancies with no active disease for ≥ 3 years.
• Prior anti-cancer treatments within 14 days or 5 half-lives (whichever is shorter) including targeted therapy, epigenetic therapy, or investigational drugs, monoclonal antibody therapy within 21 days, proteasome inhibitor therapy within 14 days, immunomodulators within 7 days, or radiotherapy (except if the radiotherapy field covers ≤5% of bone marrow).
• Known active CNS involvement or clinical evidence of myelomatous meningitis. Diagnosis of Waldenström macroglobulinemia, POEMS syndrome, or primary AL amyloidosis at screening.
• Positive for HBsAg or HBcAb with HBV DNA \>1000 copies/mL; positive for HCV antibodies, HIV antibodies, CMV DNA, syphilis, or EBV DNA.
• History of severe allergies, including anaphylaxis, or known allergy to any study drugs, their components, or murine proteins.
• Serious cardiac conditions, including but not limited to severe arrhythmias, unstable angina, recent myocardial infarction (within 6 months), NYHA Class III/IV heart failure, recent CABG, unexplained syncope, severe non-ischemic cardiomyopathy, or uncontrolled hypertension.
• Unstable systemic diseases deemed significant by the investigator, including severe liver, renal, or metabolic disorders.
• History of acute or chronic graft-versus-host disease (GVHD) or currently on immunosuppressive therapy for GVHD within 6 months prior to screening.
• Active autoimmune or inflammatory neurologic diseases such as Guillain-Barré syndrome, ALS, or clinically significant cerebrovascular diseases.
• Presence of urgent tumor-related emergencies requiring immediate treatment, such as spinal cord compression, bowel obstruction, leukostasis, or tumor lysis syndrome.
• Uncontrolled bacterial, fungal, viral, or other infections requiring antibiotics.
• Major surgery within 4 weeks prior to lymphodepletion, or planned major surgery during the study period.
• Live virus vaccinations within 4 weeks prior to screening. Severe psychiatric illness. History of alcohol or substance abuse. Pregnant or lactating women, or females and males planning to conceive within 2 years post-cell infusion.
• Any contraindication to study procedures or conditions deemed by the investigator to pose an unacceptable risk.

Sponsors & Collaborators

• Wondercel Biotech (ShenZhen): lead

Study Sites (1)

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

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

• Pengcheng He, M.D. Ph.D.

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2024
• First Posted: October 29, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2029
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)