CD19+ Leukemia, B-Cell, CD19+ Lymphoma, B-Cell
Conditions
Brief summary
Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET190L1-ARTEMIS™2 T-cells in patients with Cluster of Differentiation (CD) 19+ B cell Leukemia and Lymphoma
Detailed description
ARTEMIS™ is a novel chimeric T-cell therapy that in pre-clinical studies, functionally matches the efficacy of Chimeric Antigen Receptor (CAR) T cells, but dramatically reduces the release of cytokines upon killing of target positive tumors. The molecular target for ET190L1-ARTEMIS™ is Cluster of Differentiation 19 (CD19), which is expressed on B cell Lymphomas and B cell Leukemias. ET190L1-ARTEMIS™ is a second generation ARTEMIS™ receptor engineered with a human Fab antibody domain against CD19. This clinical study evaluates the safety and pharmacokinetics of ET190L1-ARTEMIS™ T-cells in patients with relapsed/refractory B-cell lymphoma and B-cell Leukemia.
Interventions
BIOLOGICALET190L1-ARTEMIS™ T cells -iv low dose
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 1x10\^6
BIOLOGICALET190L1-ARTEMIS™ T cells -iv middle dose
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 3x10\^6
BIOLOGICALET190L1-ARTEMIS™ T cells - iv high dose
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 10x10\^6
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
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with relapsed/refractory CD19+ B-cell lymphoma or Leukemia, with no effective therapy available per National Comprehensive Cancer Network (NCCN) guidelines * Eastern Cooperative Oncology Group (ECOG) performance status ≤2, expected survival time \> 3 months per PIs opinion * Women of childbearing age should have a negative pregnancy test and agree to use effective contraception during treatment and 1 year after the last dose. * Peripheral venous access is available and no issues with apheresis for lymphocyte isolation * serum alanine aminotransferase(ALT)\<200 Unit/L, ALT/Aspartate aminotransferase(AST)\<3 normal range; serum creatinine (Cr)\<2.5mg/dL * Voluntarily signed informed consent form
Exclusion criteria
* Women in pregnancy and lactation * Unable to perform leukapheresis and iv infusion * With active infection * Major organ failure * Patients with dependence on corticosteroids * Continuously used glucocorticoids or other immunosuppressive agents within 2 weeks * T cell deficiency or T cells are difficult to be transduced * Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of ARTEMIS T cell treatment-related adverse events | until 24 weeks | 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 ET190L1-ARTEMIS™ T T cells 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. |
| Number of ET190L1-ARTEMIS™ T cells in peripheral blood | 24 months | Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. Number of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on. |
| % of ET190L1-ARTEMIS™ T cells in peripheral blood | 24 months | Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. % of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on. |
| Maximum Tolerated Dose | 28 days up to 2 years | Determine the safety, including potential dose limiting toxicities, of the ET190L1-ARTEMIS™ T cells. A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET190L1-ARTEMIS™ T cells, which is irreversible or life threatening or CTCAE Grade 3-5. Assessed at all visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | 4 months, 1 year and 2 years | Progression free survival (PFS) |
| Median Survival（MS） | 4 months, 1 year and 2 years | Median Survival（MS） |
| Tmax of serum cytokine levels | 24 weeks | Increase or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immunoassays will be presented as time to peak level. |
| B cell depletion (Number) | 2 years | Number of B cells in peripheral blood will be presented as time to baseline level and time to recover for up to 2 years. |
| B cell depletion (%) | 2 years | % of B cells in peripheral blood will be presented as time to baseline level and time to recover for up to 2 years. |
| Overall Survival（OS） | 4 months, 1 year and 2 years | Overall Survival（OS） |
| Time to baseline for serum cytokine levels | 24 weeks | Increase or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immunoassays will be presented as time to baseline. |
| AUC of serum cytokine levels | 24 weeks | Increase or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immunoassays will be presented as area under curve (AUC). |
| Rate of disease response | 28 days to 24 months | Rate of disease response assessed by Lugano classification (a lymphoma staging classification). Response rates will be estimated as the percent of patients with any of the following: complete remission (CR), partial response (PR). |
Countries
China
Contacts
Primary ContactMei Zhang, PhD
Outcome results
None listed