Clinical trial NCT03642496: Clinical Study of ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies
Official title: The Clinical Study of Structurally Optimized ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: B-Cell Malignancies
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Eureka Therapeutics Inc.
First posted: 2018-08-22
Enrollment: 18
Sex: ALL
Minimum age (years): 6
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: Up to 12 weeks.
measure: Tmax of serum cytokine levels
timeFrame: Up to 12 weeks.
measure: Time to baseline for serum cytokine levels
timeFrame: Up to 12 weeks.
measure: Toxicity profile of ET019002T-cell treatment
timeFrame: Up to 2 years.
Secondary outcomes:
measure: Rate of disease response
timeFrame: Up to 12 weeks.
measure: Progression free survival(PFS)
timeFrame: Up to 2 years.
measure: Time to baseline for B cell level
timeFrame: Up to 2 years.
Other outcomes:
Locations:
Study officials:
affiliation: First Affiliated Hospital of Xian JiaotongUniversity
name: He Peng cheng, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.