B-Cell Malignancies
Conditions
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).
Interventions
BIOLOGICALLow 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.
BIOLOGICALMiddle 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.
BIOLOGICALHigh 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.
Sponsors
Eureka Therapeutics Inc.
First Affiliated Hospital Xi'an Jiaotong University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Contacts
Primary ContactHe Peng cheng, Doctor
Outcome results
None listed