Clinical Study of ET190L1 ARTEMIS™ in Relapsed, Refractory B Cell Lymphoma

NCT03415399 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ETCH17CD19AR103
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma, B-Cell

Keywords

relapsed/refractory CD19+ Lymphomas, B-Cell

Outcome Measures

Primary Outcomes (6)

• 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 24 months

• Toxicity profile of ET190L1 ARTEMIS™ T-cell treatment

  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™-cell 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.

  28 days up to 24 months

• Tmax of serum cytokine levels

  Increases 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 Immuoassays will be presented as time to peak level.

  24 weeks

• Time to baseline for serum cytokine levels

  Increases 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 Immuoassays will be presented as Time to baseline.

  24 weeks

• AUC of serum cytokine levels

  Increases 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 Immuoassays will be presented as area under curve (AUC).

  24 weeks

• Duration of in vivo engraftment of ET190L1 ARTEMIS™ T cells

  Number and % of ET190L1 ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and the overall exposure will be presented as area under curve (AUC).

  24 months

Secondary Outcomes (3)

• Rate of disease response

  28 days to 24 months

• Anti-tumor responses

  4 months, 1 year, 2 years

• B cell depletion

  2 years

Study Arms (1)

i.v. arm

EXPERIMENTAL

ET190L1 ARTEMIS™ T cells administered by intravenous (IV) infusion

Biological: ET190L1 ARTEMIS™ T cells

Interventions

ET190L1 ARTEMIS™ T cells BIOLOGICAL

Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) ARTEMIS™ expression construct

i.v. arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eureka Therapeutics Inc.: lead
• Peking University: collaborator

Study Sites (1)

Peking University Cancer Hospital

Beijing, 100015, China

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jun Zhu, MD

  Peking University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: January 30, 2018
• Study Start: September 9, 2017
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: March 16, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)