Universal CAR-T Cells (REVO-UWD-19) for Refractory and Relapsed B-Cell Tumors

NCT06662227 | Recruiting Early Phase 1

• 1 other identifier: 2024-REVO-UWD-19
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

B Cell Lymphoma; B Cell Leukemia; B Cell Malignancy

Keywords

CAR-T; Universal CAR-T; CD19; B cell lymphoma; B cell leukemia

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.

  [Time Frame: Within the first month post-infusion.]

• Dose-Limiting Toxicities (DLT)

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

  [Time Frame: 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-19-CAR-T cells.

  [Time Frame: From the administration of UWD-19 CAR-T cells through six months post-infusion]

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  [Time Frame: Measured at 3 and 6 months after treatment.]

• Progression-Free Survival (PFS)

  [Time Frame: From the start of treatment up to 5 years.]

• Overall Survival (OS)

  [Time Frame: From the start of treatment up to maximum follow-up period of five years.]

• Duration of Response (DOR)

  [Time Frame: From the administration of UWD-19 CAR-T cells to a maximum follow-up period of five years.]

Study Arms (1)

Off-the-shelf REVO-UWD-19

EXPERIMENTAL

Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning, followed by a one-time injection of universal UWD-19 cells

Biological: Single dose injection of certain dose of UWD-19; Drug: MMF Immunosuppression

Interventions

Single dose injection of certain dose of UWD-19 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-19 cells

Off-the-shelf REVO-UWD-19

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-19

Eligibility Criteria

• Age: 3 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wondercel Biotech (ShenZhen): lead

Study Sites (1)

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Pengcheng He, M.D. Ph.D.

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Deveopment Director

CONTACT

+8618092039190; clinical@wondercel.com

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 25, 2024
• First Posted: October 28, 2024
• Study Start: October 24, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)