Clinical Study of ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies
- Conditions
- B-Cell Malignancies
- Interventions
- Biological: Low dose ET019002- T CellsBiological: Middle dose ET019002- T CellsBiological: High dose ET019002- T Cells
- Registration Number
- NCT03642496
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 18
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description The low dose group Low dose ET019002- T Cells - The middle dose group Middle dose ET019002- T Cells - The high dose group High dose ET019002- T Cells -
- Primary Outcome Measures
Name Time Method Toxicity profile of ET019002T-cell treatment Up to 2 years. Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and ET019002 T cell related toxicity. Include but not limited to: Fever, chills, nausea, vomiting, jaundice and other gastrointestinal symptoms; Fatigue, hypotension, respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction. Assessed at all visits.
Maximum Tolerated Dose Up to 12 weeks. A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET019002T-cells,which is irreversible or life threatening or CTCAE Grade 3-5.
Tmax of serum cytokine levels Up to 12 weeks. Cytokins as measured by CBA-Bioplex Multiplex Immunoassays will be presented as time to peak level.
Time to baseline for serum cytokine levels Up to 12 weeks. Inceases or decreases in the amout of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing.
- Secondary Outcome Measures
Name Time Method Rate of disease response Up to 12 weeks. Rate of disease response assessed by lugano cliassification.Response rates will be estimated as CR,PR,SD,PD.
Progression free survival(PFS) Up to 2 years. Progression free survival(PFS) denotes the chances of staying free of disease progression for patients after treatment.
Time to baseline for B cell level Up to 2 years. B cell level as measured by Bio-Plex Multiplex Immunoassays will be presented.