Trial Title:
Universal CAR-T Cells (REVO-UWD-00B) for Refractory and Relapsed Multiple Myeloma
NCT ID:
NCT06663046
Condition:
Multiple Myleoma
Refractory and Relapsed Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Conditions: Keywords:
BCMA
REVO-U platform
Off-the-shelf CAR-T therapy
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Single dose injection of certain dose of UWD-00B
Description:
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
Arm group label:
Off-the-shelf REVO-UWD-00B
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.
Detailed description:
Multiple myeloma is a malignant plasma cell disease with high mortality rates. Patients
with relapsed and refractory cases, especially those resistant to conventional therapies
(immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies), typically
have limited survival. CAR-T cell therapy is a cutting-edge approach in which T cells are
genetically modified to target cancer cells. UWD-00B is designed to target BCMA, a
protein highly expressed on myeloma cells but minimally present in other body tissues,
making it an ideal target. Previous BCMA CAR-T therapies have shown promise, but
production limitations make universal, off-the-shelf products like UWD-00B critical for
broader patient accessibility.
Primary Objective is to evaluate the safety and initial efficacy of UWD-00B in patients
with r/r MM. The secondary Objectives is to investigate pharmacokinetic (PK) and
pharmacodynamic (PD) characteristics, including the persistence and effectiveness of
UWD-00B in targeting BCMA-positive cells. This study will enroll approximately 30
patients with relapsed or refractory MM, aged 18-75. Following preconditioning
chemotherapy to enhance CAR-T cell efficacy, patients will receive a single infusion of
UWD-00B. The study spans multiple phases, including screening, infusion, and a two-year
follow-up to assess both short- and long-term safety and efficacy.
This study hopes to provide data supporting UWD-00B as an effective, accessible treatment
for r/r MM, potentially paving the way for similar universal CAR-T therapies in other
cancers.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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%
Exclusion Criteria:
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of University of Science and Technology of China Hefei,
Address:
City:
Hefei
Country:
China
Status:
Recruiting
Contact:
Last name:
Xingbin Wang, M.D.,PhD.
Phone:
19076187801
Email:
clinical@wondercel.com
Start date:
November 30, 2024
Completion date:
December 30, 2029
Lead sponsor:
Agency:
Wondercel Biotech (ShenZhen)
Agency class:
Industry
Collaborator:
Agency:
HeFei Parasol Biotech
Agency class:
Other
Source:
Wondercel Biotech (ShenZhen)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06663046
