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

NCT ID: NCT03642496

Last Updated: 2018-08-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-19
• Study Completion Date: 2020-09-20

Brief Summary

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.

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).

Conditions

B-Cell Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The low dose group

Group Type: EXPERIMENTAL

Low dose ET019002- T Cells

Intervention Type: BIOLOGICAL

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.

The middle dose group

Group Type: EXPERIMENTAL

Middle dose ET019002- T Cells

Intervention Type: BIOLOGICAL

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.

The high dose group

Group Type: EXPERIMENTAL

High dose ET019002- T Cells

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eureka Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

He Peng cheng, Doctor

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Xian JiaotongUniversity

Central Contacts

He Peng cheng, Doctor

Role: CONTACT

hepc@163.com

0086-18991232609 ext. He Pengcheng

References

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. 2023 Jul;149(7):2757-2769. doi: 10.1007/s00432-022-04132-9. Epub 2022 Jul 1.

Reference Type: DERIVED

PMID: 35776199 (View on PubMed)

Other Identifiers

XJTU1AF2018LSL-C003

Identifier Type: -

Identifier Source: org_study_id