Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Relapsed and/or Refractory CD19-positive B Cell Hematological Malignancies Clinical Research

Inclusion Criteria43

• Age range: 6 months to 18 years old, inclusive, for both males and females.
• The patient or their guardian voluntarily signed the informed consent.
• Patients with relapsed or refractory CD19-positive B cell hematological malignancies:
• Relapsed or refractory B-ALL (meeting one of the following conditions):
• Patients who relapse within 30 months after the initial remission, with \>5% primordial cells (lymphoblast and prolymphocyte) in bone marrow morphology, confirmed by flow cytometry.
• Patients who relapse 30 months after the initial remission and fail to achieve complete remission or show poor response to early treatment after one course of standardized induction therapy.
• Patients who relapse after allogeneic hematopoietic stem cell transplantation (HSCT) and must undergo screening 3 months post-HSCT .
• Patients who do not achieve CR after standardized chemotherapy, or have \>1% minimal residual disease (MRD) in bone marrow after 3 months of chemotherapy.
• Philadelphia-chromosome-positive (Ph+) patients who do not achieve CR or relapse after being treated with at least two tyrosine kinase inhibitors (TKI).
• Patients who are not suitable candidates for allogeneic hematopoietic stem cell transplantation.
• Relapsed or refractory CD19+ B-NHL (meeting one of the following conditions):
• Patients who have been treated with CD20 antibodies (such as rituximab) and at least two chemotherapy regiments, one of which should include anthracyclines.
• After these treatments, patients experienced stable disease (SD) (with SD duration ≤12 months) or disease progression.
• Patients who relapse after auto/allo-HSCT, or are not eligible for HSCT.
• Patients with double-hit and triple-hit lymphoma who do not respond to second-line treatment.
• Positive CD19 expression comfirmed by immunohistochemistry or flow cytometry.
• For participants who had failed prior CD19-CAR T cell therapy: at least 30-days has elapsed since participant received last CD19-CAR T cell therapy.
• Presence at least one measurable lesion at baseline, as per the initial assessment, staging and response assessment recommendations for Hodgkin's and non-Hodgkin's lymphoma (2014 edition).
• Life expectancy ≥ 12 weeks.
• ECOG ≤ 1.
• Organ function:
• Complete blood count (CBC) test results should meet the following criteria within 24 hours before apheresis (Avoid blood/platelet transfusion, cell growth factors (except recombinant erythropoietin) and other supportive treatments within 7 days prior to the test):
• Absolute Lymphocyte Count (ALC) ≥ 0.5×10\^9 /L (except for those receiving bridging chemotherapy).
• Platelet (PLT) ≥ 25×10\^9 /L.
• Hemoglobin (Hb) ≥ 70.0 g/L
• Blood biochemistry:
• Serum creatinine (Scr) ≤ 1.5× Upper limit of normal (ULN), or Creatinine Clearance (Ccr) ≥ 40 mL/min (calculated using the Cockcroft-Gault formula).
• Alanine aminotransferase (ALT) ≤ 2.5×ULN.
• Aspartate aminotransferase (AST) ≤ 2.5×ULN.
• Total bilirubin (TBIL) ≤ 2×ULN; Patients who with Gilbert-Meulengracht syndrome with TBIL ≤ 3×ULN and Direct Bilirubin (DBIL) ≤1.5×ULN may be included.
• Amylase (AMY) and Lipase (LPS) ≤ 1.5×ULN.
• Alkaline phosphatase (ALP) ≤ 2.5×ULN.
• If bone or liver metastases are present, AST, ALT, ALP ≤ 5×ULN.
• Prothrombin time (PT) was extended ≤ 4 s, fibrinogen ≥ 1 g/L, activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
• Pulmonary function: dyspnea ≤ CTCAE grade 1 and blood oxygen saturation (SaO2) ≥ 91% in ambient air.
• Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) with a left ventricular ejection fraction (LVEF) ≥ 45％.
• Patients taking the following medications must meet the following criteria:
• Steroids: Therapeutic doses of steroids must be discontinued 2 weeks prior to Meta10-19 infusion. However, physiological replacement doses of steroids are permitted, with hydrocortisone or its equivalent \< 6-12mg/mm\^2/day.
• Immunosuppressive agents: Any immunosuppressive medication must be stopped ≥ 4 weeks before signing the informed consent.
• Anti-proliferative therapy other than preconditioning chemotherapy should be ceased within 2 weeks prior to Meta10-19 infusion.
• Treatment for central nervous system (CNS) diseases must be stopped 1 week before Meta10-19 infusion (e.g., intrathecal methotrexate).
• As determined by the researchers, patients who have recovered from the toxicity of the previous treatments, that is, the CTCAE toxicity grade is less than 1 (excluding specific toxicity of grade 2 or lower, such as hair loss, deemed irrecoverable in a short timeframe by the researchers) are suitable for receiving pretreatment chemotherapy and CAR-T cell therapy.
• The patient should have adequate venous access for apheresis or peripheral blood collection, with no other contraindications for blood cell separation.