Clinical trial NCT03415399: Clinical Study of ET190L1 ARTEMIS™ in Relapsed, Refractory B Cell Lymphoma
Official title: Phase 1, Open-label, Single-arm, Dose-escalation Clinical Study Evaluating the Safety and Efficacy of ET190L1 ARTEMIS™ (Anti-CD19-ARTEMIS™) in Relapsed, Refractory B Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, B-Cell
Keywords: relapsed/refractory CD19+ Lymphomas, B-Cell
Lead sponsor: Eureka Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Peking University
First posted: 2018-01-30
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is to determine the safety, including potential dose limiting toxicities, of ET190L1 ARTEMIS™ T cells and the duration of in vivo survival of ET190L1 ARTEMIS™ T cells in patients with relasped/refractory B-cell lymphoma. For patients with detectable disease, the study will also measure anti-tumor responses after ET190L1 ARTEMIS™ cell infusions.

Detailed description: ET190L ARTEMIS™ 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.

Eligibility criteria: Inclusion Criteria:

* Patients with relapsed/refractory CD19+ B-cell lymphoma, with no effective therapy available per NCCN guidelines
* No HCV, HIV infection, no active HBV
* Liver and kidney function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) does not exceed five times the upper limit of normal range. ALT \<200U / L, bilirubin \<2.0 mg/ dL
* Renal function: creatinine \<2.5mg / dL; Pre-treatment absolute creatinine clearance ≥50 mL / minute
* CBC: Hemoglobin ≥ 80g / L, Absolute Neutrophil Counts ≥1 × 10\^9 / L, Platelets ≥50 × 10\^9 / L
* Echocardiography or multiple gated angiogram (MUGA) ejection fraction\> 45%
* 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.
* Had a recurrence after at least a first-line systemic treatment
* Peripheral venous access is available and no issues with apheresis for lymphocyte isolation
* 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
* Continuously used glucocorticoids or other immunosuppressive agents within 4 weeks
* T cell deficiency or T cells are difficult to be transduced

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 28 days up to 24 months
measure: Toxicity profile of ET190L1 ARTEMIS™ T-cell treatment
timeFrame: 28 days up to 24 months
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: Duration of in vivo engraftment of ET190L1 ARTEMIS™ T cells
timeFrame: 24 months
Secondary outcomes:
measure: Rate of disease response
timeFrame: 28 days to 24 months
measure: Anti-tumor responses
timeFrame: 4 months, 1 year, 2 years
measure: B cell depletion
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
Study officials:
affiliation: Peking University
name: Jun Zhu, MD
role: PRINCIPAL_INVESTIGATOR
References: