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

Xi'an Jiaotong University

Status and phase: Unknown; Early Phase 1

Conditions: B-Cell Malignancies

Treatments: Biological: Middle dose ET019002- T Cells; Biological: High dose ET019002- T Cells; Biological: Low dose ET019002- T Cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03642496

XJTU1AF2018LSL-C003

Details and patient eligibility

About

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.

Full 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).

Enrollment: 18 estimated patients

Sex: All

Ages: 6 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

The low dose group

Experimental group

Treatment:

Biological: Low dose ET019002- T Cells

The middle dose group

Experimental group

Treatment:

Biological: Middle dose ET019002- T Cells

The high dose group

Experimental group

Treatment:

Biological: High dose ET019002- T Cells