CD19+ Leukemia, B-Cell Clinical Trial
Official title:
Phase 1, Open-label, Single-arm, Dose-escalation Clinical Study Evaluating the Safety and Efficacy of ET190L1-ARTEMIS™2 in Relapsed, Refractory B Cell Leukemia and Lymphoma
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
| Status | Recruiting |
| Enrollment | 18 |
| Est. completion date | December 6, 2019 |
| Est. primary completion date | December 6, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility |
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) |
| Country | Name | City | State |
|---|---|---|---|
| China | First Affiliated Hospital of Xi'an Jiaotong University | Xi'an |
| Lead Sponsor | Collaborator |
|---|---|
| First Affiliated Hospital Xi'an Jiaotong University | Eureka Therapeutics Inc. |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Frequency of ARTEMIS T cell treatment-related adverse events | 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. | until 24 weeks | |
| Primary | Number of ET190L1-ARTEMIS™ T cells in peripheral blood | 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. | 24 months | |
| Primary | % of ET190L1-ARTEMIS™ T cells in peripheral blood | 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. | 24 months | |
| Primary | Maximum Tolerated Dose | 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. | 28 days up to 2 years | |
| Secondary | Tmax of serum cytokine levels | 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. | 24 weeks | |
| Secondary | Time to baseline for serum cytokine levels | 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. | 24 weeks | |
| Secondary | AUC of serum cytokine levels | 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). | 24 weeks | |
| Secondary | Rate of disease response | 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). | 28 days to 24 months | |
| Secondary | Progression free survival (PFS) | Progression free survival (PFS) | 4 months, 1 year and 2 years | |
| Secondary | Median Survival(MS) | Median Survival(MS) | 4 months, 1 year and 2 years | |
| Secondary | Overall Survival(OS) | Overall Survival(OS) | 4 months, 1 year and 2 years | |
| Secondary | B cell depletion (Number) | Number of B cells in peripheral blood will be presented as time to baseline level and time to recover for up to 2 years. | 2 years | |
| Secondary | B cell depletion (%) | % of B cells in peripheral blood will be presented as time to baseline level and time to recover for up to 2 years. | 2 years |