Clinical Study of ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies

The Clinical Study of Structurally Optimized ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies

This study is to determine the safety, including potential dose limiting toxicities, and efficiency of ET019002-T cells and the duration of in vivo survival of ET019002-T cells in patients with relapsed/refractory B-Cell Malignancies.

Study Overview

• Status: Unknown
• Conditions: B-Cell Malignancies
• Intervention / Treatment: Biological: Low dose ET019002- T Cells; Biological: Middle dose ET019002- T Cells; Biological: High dose ET019002- T Cells

Detailed Description

ET019002-T cell therapy 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.The arm of the study is experimental i.v. arm:ET019002-T cells administered by intravenous (IV) infusion.The intervention is ET019002-T cells(Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET019002)-expression construct).

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Early Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed B cell malignancies including: B-cell Acute Lymphoblastic Leukemia (B-ALL) and B cell lymphomas (DLBCL、FL、MZL、LPL、HCL、CLL、BL、MCL)
• Refractory/Relapsed B cell malignancies:
• Age 6-80 years, male or female
• Nidus could be evaluated: minimum diameter of single nidus ≥10mm, and/or tumor cells in bone marrow ≥ 5%
• ECOG≤2 points
• Function of main organs or tissues were functional: Liver - ALT/AST≤3 normal upper limit, Serum total bilirubin (TBIL) ≤2 normal upper limit; Kidney - glomerular filtration rate (GFR) > 60 mL/min/1.73 m2 or serum creatinine in normal range; Lunge - carbon monoxide diffusion capacity (DLCO) or forced expiratory volume in 1s (FEV) >45% estimate; Heart - left ventricular ejection fraction (LVEF) ≥50%
• Expecting life span ≥3 months
• No chemotherapy, radiation therapy or immunotherapy in 2 weeks before enrollment
• Fertile females/males consented to use contraceptives during participation of the trial
• Patient or his/her custodia could understand and is willing to sign the written consent

Exclusion Criteria:

• Pregnancy or lactation
• Couldn't use contraceptives during participation of the trial
• Couldn't collect enough monocyte
• Active and/or severe infection
• HIV infection, active Hepatitis B or Hepatitis C infection
• Had active autoimmune disease
• Had non-melanoma skin carcinoma (NMSC) or Carcinoma in situ (e.g. cervix, bladder, galactophore)
• Obvious clinical encephalopathy or novel neuron function damage
• Organ failure: Heart - upper than NYHA level III or had uncontrolled malignant arrhythmia; Liver - upper than level III of Wuhan conference classification; Kidney - kidney failure stage3 or worse
• Using immunosuppressive drugs or adreno-cortical hormone (ACH) within two weeks of enrollment
• Insufficient T cell number or T cell transfection rate
• Needed urgent disease controlling due to tumor load
• Patients had biological treatment, immunotherapy or radiation therapy within 6 weeks prior to enrollment or are currently under these treatment
• Substance abuse or drug addiction
• lack of compliance, communication deficit or other unaccommodated situations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The low dose group	Biological: Low dose ET019002- T Cells; ET019002- T Cells are autologous T cells transduced expressing a novel anti-CD19 (ET019002) chimeric antigen receptor,and are administered by intravenous infusion with the dose of 0.75×10*6/kg.
Experimental: The middle dose group	Biological: Middle dose ET019002- T Cells; ET019002- T Cells are autologous T cells transduced expressing a novel anti-CD19 (ET019002) chimeric antigen receptor,and are administered by intravenous infusion with the dose of 1.5×10*6/kg.
Experimental: The high dose group	Biological: High dose ET019002- T Cells; ET019002- T Cells are autologous T cells transduced expressing a novel anti-CD19 (ET019002) chimeric antigen receptor,and are administered by intravenous infusion with the dose of 3.0×10*6/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET019002T-cells,which is irreversible or life threatening or CTCAE Grade 3-5.	Up to 12 weeks.
Tmax of serum cytokine levels	Cytokins as measured by CBA-Bioplex Multiplex Immunoassays will be presented as time to peak level.	Up to 12 weeks.
Time to baseline for serum cytokine levels	Inceases or decreases in the amout of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing.	Up to 12 weeks.
Toxicity profile of ET019002T-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 ET019002 T cell 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.	Up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of disease response	Rate of disease response assessed by lugano cliassification.Response rates will be estimated as CR,PR,SD,PD.	Up to 12 weeks.
Progression free survival(PFS)	Progression free survival(PFS) denotes the chances of staying free of disease progression for patients after treatment.	Up to 2 years.
Time to baseline for B cell level	B cell level as measured by Bio-Plex Multiplex Immunoassays will be presented.	Up to 2 years.

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Eureka Therapeutics Inc.
• Investigators: Principal Investigator: He Peng cheng, Doctor, First Affiliated Hospital of Xian JiaotongUniversity

Publications and helpful links

General Publications

• He P, Liu H, Zimdahl B, Wang J, Luo M, Chang Q, Tian F, Ni F, Yu D, Liu H, Chen L, Wang H, Zhang M, Grupp SA, Liu C. A novel antibody-TCR (AbTCR) T-cell therapy is safe and effective against CD19-positive relapsed/refractory B-cell lymphoma. J Cancer Res Clin Oncol. 2022 Jul 1. doi: 10.1007/s00432-022-04132-9. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 19, 2018
• Primary Completion (Anticipated): August 19, 2020
• Study Completion (Anticipated): September 20, 2020

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: August 20, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: XJTU1AF2018LSL-C003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No