Clinical Study of ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies

The Clinical Study of Structurally Optimized ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies

This study is to determine the safety, including potential dose limiting toxicities, and efficiency of ET019002-T cells and the duration of in vivo survival of ET019002-T cells in patients with relapsed/refractory B-Cell Malignancies.

ET019002-T cell therapy is a novel chimeric T-cell therapy platform that in preclinical studies, functionally matches the efficacy of CAR-T cells, but dramatically reduces the release of cytokines upon killing of target-positive tumors.The arm of the study is experimental i.v. arm:ET019002-T cells administered by intravenous (IV) infusion.The intervention is ET019002-T cells(Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET019002)-expression construct).

Inclusion Criteria:

• Diagnosed B cell malignancies including: B-cell Acute Lymphoblastic Leukemia (B-ALL) and B cell lymphomas (DLBCL、FL、MZL、LPL、HCL、CLL、BL、MCL)
• Refractory/Relapsed B cell malignancies:
• Age 6-80 years, male or female
• Nidus could be evaluated: minimum diameter of single nidus ≥10mm, and/or tumor cells in bone marrow ≥ 5%
• ECOG≤2 points
• Function of main organs or tissues were functional: Liver - ALT/AST≤3 normal upper limit, Serum total bilirubin (TBIL) ≤2 normal upper limit; Kidney - glomerular filtration rate (GFR) > 60 mL/min/1.73 m2 or serum creatinine in normal range; Lunge - carbon monoxide diffusion capacity (DLCO) or forced expiratory volume in 1s (FEV) >45% estimate; Heart - left ventricular ejection fraction (LVEF) ≥50%
• Expecting life span ≥3 months
• No chemotherapy, radiation therapy or immunotherapy in 2 weeks before enrollment
• Fertile females/males consented to use contraceptives during participation of the trial
• Patient or his/her custodia could understand and is willing to sign the written consent

Exclusion Criteria:

• Pregnancy or lactation
• Couldn't use contraceptives during participation of the trial
• Couldn't collect enough monocyte
• Active and/or severe infection
• HIV infection, active Hepatitis B or Hepatitis C infection
• Had active autoimmune disease
• Had non-melanoma skin carcinoma (NMSC) or Carcinoma in situ (e.g. cervix, bladder, galactophore)
• Obvious clinical encephalopathy or novel neuron function damage
• Organ failure: Heart - upper than NYHA level III or had uncontrolled malignant arrhythmia; Liver - upper than level III of Wuhan conference classification; Kidney - kidney failure stage3 or worse
• Using immunosuppressive drugs or adreno-cortical hormone (ACH) within two weeks of enrollment
• Insufficient T cell number or T cell transfection rate
• Needed urgent disease controlling due to tumor load
• Patients had biological treatment, immunotherapy or radiation therapy within 6 weeks prior to enrollment or are currently under these treatment
• Substance abuse or drug addiction
• lack of compliance, communication deficit or other unaccommodated situations