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

NCT03642496 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: XJTU1AF2018LSL-C003
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

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.

Conditions

B-Cell Malignancies

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Rate of disease response

  Up to 12 weeks.

• Progression free survival(PFS)

  Up to 2 years.

• Time to baseline for B cell level

  Up to 2 years.

Study Arms (3)

The low dose group

EXPERIMENTAL

Biological: Low dose ET019002- T Cells

The middle dose group

EXPERIMENTAL

Biological: Middle dose ET019002- T Cells

The high dose group

EXPERIMENTAL

Biological: High dose ET019002- T Cells

Interventions

Low dose ET019002- T Cells 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 low dose group

Middle dose ET019002- T Cells 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 middle dose group

High dose ET019002- T Cells 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.

The high dose group

Eligibility Criteria

• Age: 6 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead
• Eureka Therapeutics Inc.: collaborator

Related Publications (1)

• 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.

  PMID: 35776199 DERIVED

Study Officials

• He Peng cheng, Doctor

  First Affiliated Hospital of Xian JiaotongUniversity

  PRINCIPAL INVESTIGATOR

Central Study Contacts

He Peng cheng, Doctor

CONTACT

0086-18991232609; hepc@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 22, 2018
• Study Start: August 19, 2018
• Primary Completion: August 19, 2020
• Study Completion: September 20, 2020
• Last Updated: August 23, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share