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

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.

Eligibility

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.

Conditions4

Browse More Trials