Clinical trial NCT03895944: ET190L1-ARTEMIS™ T Cells in Relapsed, Refractory B Cell Leukemia and Lymphoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: CD19+ Lymphoma, B-Cell
CD19+ Leukemia, B-Cell
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Eureka Therapeutics Inc.
First posted: 2019-03-29
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Frequency of ARTEMIS T cell treatment-related adverse events
timeFrame: until 24 weeks
measure: Number of ET190L1-ARTEMIS™ T cells in peripheral blood
timeFrame: 24 months
measure: % of ET190L1-ARTEMIS™ T cells in peripheral blood
timeFrame: 24 months
measure: Maximum Tolerated Dose
timeFrame: 28 days up to 2 years
Secondary outcomes:
measure: Tmax of serum cytokine levels
timeFrame: 24 weeks
measure: Time to baseline for serum cytokine levels
timeFrame: 24 weeks
measure: AUC of serum cytokine levels
timeFrame: 24 weeks
measure: Rate of disease response
timeFrame: 28 days to 24 months
measure: Progression free survival (PFS)
timeFrame: 4 months, 1 year and 2 years
measure: Median Survival（MS）
timeFrame: 4 months, 1 year and 2 years
measure: Overall Survival（OS）
timeFrame: 4 months, 1 year and 2 years
measure: B cell depletion (Number)
timeFrame: 2 years
measure: B cell depletion (%)
timeFrame: 2 years
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Mei Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
References: