Clinical Study of ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: The low dose group
|
Biological: Low dose ET019002- T Cells
ET019002- T Cells are autologous T cells transduced expressing a novel anti-CD19 (ET019002) chimeric antigen receptor,and are administered by intravenous infusion with the dose of 0.75×10*6/kg.
|
| Experimental: The middle dose group
|
Biological: Middle dose ET019002- T Cells
ET019002- T Cells are autologous T cells transduced expressing a novel anti-CD19 (ET019002) chimeric antigen receptor,and are administered by intravenous infusion with the dose of 1.5×10*6/kg.
|
| Experimental: The high dose group
|
Biological: High dose ET019002- T Cells
ET019002- T Cells are autologous T cells transduced expressing a novel anti-CD19 (ET019002) chimeric antigen receptor,and are administered by intravenous infusion with the dose of 3.0×10*6/kg.
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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)
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Refractory/Relapsed B cell malignancies:
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Age 6-80 years, male or female
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Nidus could be evaluated: minimum diameter of single nidus ≥10mm, and/or tumor cells in bone marrow ≥ 5%
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ECOG≤2 points
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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%
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Expecting life span ≥3 months
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No chemotherapy, radiation therapy or immunotherapy in 2 weeks before enrollment
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Fertile females/males consented to use contraceptives during participation of the trial
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Patient or his/her custodia could understand and is willing to sign the written consent
Exclusion Criteria:
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Pregnancy or lactation
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Couldn't use contraceptives during participation of the trial
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Couldn't collect enough monocyte
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Active and/or severe infection
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HIV infection, active Hepatitis B or Hepatitis C infection
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Had active autoimmune disease
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Had non-melanoma skin carcinoma (NMSC) or Carcinoma in situ (e.g. cervix, bladder, galactophore)
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Obvious clinical encephalopathy or novel neuron function damage
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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
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Using immunosuppressive drugs or adreno-cortical hormone (ACH) within two weeks of enrollment
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Insufficient T cell number or T cell transfection rate
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Needed urgent disease controlling due to tumor load
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Patients had biological treatment, immunotherapy or radiation therapy within 6 weeks prior to enrollment or are currently under these treatment
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Substance abuse or drug addiction
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lack of compliance, communication deficit or other unaccommodated situations
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- First Affiliated Hospital Xi'an Jiaotong University
- Eureka Therapeutics Inc.
Investigators
- Principal Investigator: He Peng cheng, Doctor, First Affiliated Hospital of Xian JiaotongUniversity
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XJTU1AF2018LSL-C003