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

B-Cell Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03642496
• Other study ID #: XJTU1AF2018LSL-C003
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: August 19, 2018
• Est. completion date: September 20, 2020

Study information

• Verified date: July 2018
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: He Peng cheng, Doctor
• Phone: 0086-18991232609
• Email: hepc[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: September 20, 2020
• Est. primary completion date: August 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• B-Cell Malignancies
• Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University	Eureka Therapeutics Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	Time to baseline for B cell level	B cell level as measured by Bio-Plex Multiplex Immunoassays will be presented.	Up to 2 years.