Overview

A Study of Metabolically Armed CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma

Eligibility

Inclusion Criteria:

• The patient or his/her guardian voluntarily signed the informed consent
• Adult Patients clinical diagnosis of relapsed and refractory diffuse large B-cell lymphoma (Primary mediastinal large B-cell lymphoma and transformed follicular lymphoma are included)

Definition of refractory:

1. No response to the last treatment, including:

   The best response to the last treatment was PD, or ; The best response to the last treatment was SD and the duration was not more than 6 months after the last dose.

2. Not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including:

        Disease progression or recurrence within 12 months or less (recurrence must be confirmed by
        biopsy) after ASCT treatment, or; Patients accept remedial treatment after ASCT must have
        no response or relapse after the last treatment
          -  Patients who had previously received ≥2 lines therapy including at least:
               1. A chemotherapy regimen containing anthracyclines
               2. For patients with transformed DLBCL from follicular lymphoma, they must have
                  previously received chemotherapy for follicular lymphoma and have refractory
                  disease after transformation to DLBCL.
          -  Patients with double-strike and triple-strike lymphoma who do not respond to
             second-line treatment, where double-strike/triple-strike is defined as:
        Detection of lymphoma cells with C-MYC gene translocation accompanied by BCL-2 gene
        translocation or/and BCL-6 gene translocation by chromosome or FISH technology.
          -  CD19 expression was positive by immunohistochemistry or flow cytometry (accept the
             results of this peripheral blood mononuclear cells or previous report from a Class A
             tertiary hospital before peripheral blood collection)
          -  At least one measurable lesion at baseline, according to the initial assessment,
             staging and Response Assessment recommendations for Hodgkin's and non-Hodgkin's
             lymphoma (2014 edition)
          -  Expected survival time greater than 12 weeks
          -  The baseline ECOG score was 0 or 1
          -  Organ function:
               1. Kidney function is defined as:
                  Serum creatinine ≤1.5 times ULN, or; The glomerular filtration rate (eGFR)
                  estimated by MDRD formula was ≥60m/ min/1.73m2; [eGFR=186×(age)-0.203×SCr- 1.
                  154(mg/dl), for females, the result was ×0.742]
               2. Liver function is defined as:
                  ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with
                  Gilbert-Meulengracht syndrome. Patients with Gilbert-Meulengracht syndrome with
                  total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included
               3. Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2)
                  ≥91% in indoor air environment.
          -  Hemodynamic stability was determined by echocardiography or multichannel radionuclide
             angiography (MUGA) and LVEF ≥45%
          -  Patients using the following drugs must meet the following conditions:
               1. Steroid: Therapeutic doses of steroids must be discontinued 2 weeks prior to
                  Meta10-19 infusion. However, physiological replacement doses of steroids are
                  permitted, hydrocortisone or its equivalent <6-12mg/mm2/ day
               2. Immunosuppressive agent: Any immunosuppressive drug must be stopped ≥4 weeks
                  before the informed consent is signed
               3. Anti-proliferative therapy in addition to preconditioning chemotherapy 2 weeks
                  prior to Meta10-19 infusion
               4. Treatment for CNS disease must be stopped 1 week before Meta10- 19 infusion
                  (e.g., intrathecal methotrexate)
          -  The patient has recovered from the toxicity of the previous treatment, that is, the
             CTCAE toxicity grade is less than 1 (The exception is specific toxicity of grade 2 or
             less, such as hair loss, which the researchers have determined is not recoverable in a
             short period of time) is suitable for pretreatment chemotherapy and CAR T cell therapy
          -  Women of childbearing age and all male patients must consent to use a effective
             contraception for at least 12 months after Meta10-19 infusion and until two
             consecutive PCR tests show no more CAR T cells in vivo
        Exclusion Criteria:
          -  Patients with present or history of central nervous system diseases such as seizures
             disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any
             autoimmune disease with CNS involvement
          -  Patients with history of allogeneic hematopoietic stem cell transplantation
          -  Patients who had received chemotherapy other than preconditioning chemotherapy within
             2 weeks prior to Meta10-19 infusion
          -  Patients who participated in other clinical trials within 30 days prior to enrollment
          -  Patients with active hepatitis B (defined as hepatitis B surface antigen positive or
             hepatitis B core antibody positive, concomitant hepatitis B virus DNA level >1000
             copies/ml) or hepatitis C (HCV RNA positive)
          -  Patients with HIV antibody positive or treponema pallidum antibody positive
          -  Patients with uncontrolled acute life-threatening bacterial, viral or fungal
             infections (e.g. positive blood cultures ≤72 hours before Meta10-19infusion)
          -  Patients with unstable angina pectoris and/or myocardial infarction within 6 months
             prior to enrollment
          -  Patients with history of other malignancies, but the following conditions can be
             enrollment:
               1. Adequately treated basal or squamous cell carcinoma (requiring adequate wound
                  healing before signing informed consent);
               2. Carcinoma in situ (DCIS) of cervical or breast cancer, which has been treated
                  therapeutically, has shown no signs of recurrence for at least 3 years prior to
                  the signing of the informed consent
               3. The primary malignancy has been completely resected and in complete remission for
                  ≥5 years
          -  Women who are pregnant or breastfeeding (pregnancy tests for women of childbearing age
             are positive)
          -  Patients with active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre
             syndrome, amyotrophic lateral sclerosis);
          -  Other conditions that the investigator considered should not be enrolled in this
             clinical study, such as poor compliance.