Trial Title:
Universal CAR-T Cells (REVO-UWD-19) for Refractory and Relapsed B-Cell Tumors
NCT ID:
NCT06662227
Condition:
B Cell Lymphoma
B Cell Leukemia
B Cell Malignancy
Conditions: Official terms:
Lymphoma, B-Cell
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Conditions: Keywords:
CAR-T
Universal CAR-T
CD19
B cell lymphoma
B cell leukemia
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-19
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-19 cells
Arm group label:
Off-the-shelf REVO-UWD-19
Summary:
This study is a single-arm, single-center, investigator-initiated clinical trial. The
primary objective is to evaluate the safety and preliminary efficacy of administering
universal CD19 CAR-T cells to subjects with refractory and relapsed B-cell tumors.
Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning after
signing an informed consent form, followed by a one-time injection of universal UWD-19 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:
This study is a single-arm clinical trial evaluating the universal CD19-targeted CAR-T
cell therapy (UWD-CD19) in treating relapsed and refractory B-cell tumors. Initiated by
investigators, the study aims to assess the safety and preliminary efficacy of this cell
therapy, providing new therapeutic options for patients with B-cell tumors-a class of
hematologic malignancies that often recur and resist standard treatments, posing
substantial treatment challenges.
CD19 is a specific marker predominantly expressed on the surface of B-cells, making it a
prime target for CAR-T cell therapies. CAR-T therapy involves extracting T cells from a
healthy donor and genetically engineering them to recognize and attack CD19-expressing
tumor cells. UWD-CD19, a "universal" CAR-T cell product, seeks to enhance therapy
adaptability, allowing it to effectively target B-cell tumors across different patient
groups.
Study Objectives The primary objective of this study is to observe the therapeutic
response in patients with relapsed or refractory B-cell tumors through a single infusion
of UWD-CD19, specifically focusing on safety, tolerability, and preliminary efficacy. The
research team will also conduct long-term follow-up on patients to assess the durability
of treatment effects and survival rates, providing data support for the potential wider
application of this novel therapy.
Inclusion Criteria: Patients aged between 3 and 70, with no gender restrictions, must
meet diagnostic criteria for B-cell lymphoma with CD19-positive tumor cells. Patients
should have an evaluable or measurable lesion as defined by the 2014 Lugano criteria.
Preconditioning: Eligible patients will receive lymphodepleting chemotherapy with
Fludarabine and Cyclophosphamide before cell infusion to suppress the immune system and
optimize CAR-T cell performance.
CAR-T Cell Infusion: Patients will receive a one-time infusion of UWD-CD19 cells, and
their responses will be closely monitored during and after infusion to ensure safety.
Follow-up and Efficacy Assessment: Following treatment, patients will be hospitalized for
a period and, after discharge, return regularly for follow-up and efficacy evaluations.
The research team will conduct survival monitoring for at least five years.
Inclusion and Exclusion Criteria To ensure the study's safety and scientific rigor,
strict inclusion and exclusion criteria are set. Patients must meet requirements across
age, pathology, disease stage, and organ function, and should not have other severe
health conditions (e.g., active CNS involvement, severe cardiovascular disease, serious
infections) that could confound efficacy assessments or increase patient risk.
Potential Impact If results demonstrate good safety and efficacy of UWD-CD19 cell therapy
in patients with relapsed and refractory B-cell tumors, this could open a new treatment
pathway for this patient population. Universal CAR-T cell therapy could eventually extend
to more hematologic malignancies, offering hope and support to patients facing
significant treatment barriers.
Ethics and Risk Management The study has been approved by the Medical Ethics Committee,
and the research team will strictly adhere to ethical standards, ensuring patients
provide informed consent and receive adequate medical support. Since CAR-T therapy may
present potential side effects (e.g., cytokine release syndrome, neurotoxicity), patients
will be under real-time monitoring, with prompt intervention provided as needed.
This study aims to provide new insights and therapeutic approaches for B-cell tumor
treatment through an in-depth evaluation of UWD-CD19 cell therapy. The research team will
continue observing and recording patients' responses, establishing a scientific
foundation for future immunotherapies in oncology and offering patients the prospect of
long-term health benefits and quality of life improvements.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients (or their guardians) understand the study and voluntarily sign the informed
consent form, with an expected ability to complete follow-up evaluations and
treatments as per study protocol.
Age range: 3-70 years, no gender restrictions. Diagnosis of B-cell lymphoma, meeting the
2018 NCCN B-Cell Lymphoma guidelines (Version 5), with CD19 positivity confirmed by flow
cytometry or immunohistochemistry.
At least one evaluable or measurable lesion per Lugano 2014 criteria. Evaluable lesions
are indicated by FDG uptake above liver levels on FDG/PET or by lymphoma-like
characteristics on PET/CT. Measurable lesions require a nodal diameter >15 mm or
extranodal lesion >10 mm (with post-radiation evidence of progression if previously
irradiated). Cases without measurable lesions but with diffuse liver FDG uptake are
excluded.
Refractory and relapsed B-cell lymphoma, meeting at least one of the following: a.
Received ≥2 cycles of standardized second-line or higher treatment, and meets Lugano 2014
criteria for best clinical response:
Progressive Disease (PD) on the most recent treatment.
Stable Disease (SD) lasting <6 months before progressing. b. Recurrence or progression
≤12 months post-autologous stem cell transplant. c. Based on investigator judgment, the
potential benefit may outweigh risk in cases such as:
Recent SD with measurable disease progression but not meeting PD criteria. Partial
remission (PR) or better lasting <6 months post-treatment, then progression.
Intolerance to most recent chemotherapy. Relapsed/refractory CD19-positive acute B
lymphoblastic leukemia.
Laboratory values indicating adequate organ and marrow function, with no severe cardiac,
pulmonary, hepatic, renal, or immune dysfunction:
Serum albumin ≥25 g/L Creatinine clearance ≥30 mL/min/1.73 m² ALT and AST ≤3.0× ULN Total
bilirubin ≤2.0× ULN (exceptions for congenital hyperbilirubinemia like Gilbert syndrome
with direct bilirubin ≤1.5× ULN) PT and APTT <2× ULN Oxygen saturation ≥95% Blood
transfusions allowed to maintain hemoglobin ≥8.0 g/dL. ECOG performance status 0-1.
Expected survival time >90 days. Negative β-hCG test for women of childbearing potential
at screening and prior to chemotherapy.
Women of childbearing potential must use a highly effective contraceptive method (annual
failure rate <1%) from the time of consent until 1 year after UWD-CD19 infusion,
including:
Non-user-dependent: implantable progestogen, IUD, hormone-releasing system, or partner
vasectomy.
User-dependent: combination hormonal contraception, progestogen-only pill, or injection.
Exclusion Criteria:
- History of aggressive malignancies other than B-cell lymphoma, except:
Cancer in remission >2 years post-curative therapy. Non-melanoma skin cancer successfully
treated and inactive.
Prior anti-cancer therapy including:
Targeted, epigenetic, or experimental drug therapy within 14 days or 5 half-lives.
Cytotoxic therapy within 14 days. Immunomodulators within 7 days. Monoclonal antibodies
within 21 days. Radiotherapy within 14 days. Active CNS involvement. Conditions like
Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.
Active hepatitis B (HBsAg or HBcAb positive with viral load >1000 copies/ml), hepatitis C
(HCV RNA positive), HIV, CMV, or syphilis positivity.
Severe allergy history, or known allergy to trial components, adjuvants, or
animal-derived proteins.
Severe cardiac conditions such as arrhythmias, unstable angina, recent MI, heart failure
(NYHA III/IV), uncontrolled hypertension.
Unstable systemic disease, including significant liver, kidney, or metabolic disease
requiring medication.
Acute/chronic GVHD or requiring immunosuppressants within 6 months. Active autoimmune or
inflammatory neurologic diseases. Urgent tumor-related conditions requiring emergency
treatment. Uncontrolled bacterial, fungal, or viral infections. Major surgery within 4
weeks or planned major surgery during the study. Live virus vaccination within 4 weeks
prior to screening. Severe psychiatric disorders. History of substance abuse. Pregnant or
lactating women, or individuals planning conception within 2 years of cell infusion.
Any contraindications per investigator's judgment due to clinical standards or patient's
condition.
Gender:
All
Minimum age:
3 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of University of Science and Technology of China
Address:
City:
Hefei
Country:
China
Status:
Recruiting
Contact:
Last name:
Xingbin Wang, M.D.,PhD.
Phone:
+8619076187801
Email:
clinical@wondercel.com
Start date:
October 24, 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/NCT06662227
