Individualized Tumor Specific TCR- T Cells in the Treatment of Advanced Solid Tumors

Official title

An Open, Single-center, Stage I Clinical Study of Individualized Tumor Specific TCR-T Cells in the Treatment of Advanced Solid Tumors.

Overview

The primary purpose of this study is to evaluate the safety of the tumor-specific TCR-T cells in the treatment of advanced Solid Tumor . The secondary purpose of this study is to preliminarily showed the effect of TCR-T cells in the treatment of advanced Solid Tumor .

Detailed description

This study is an open, single-center, phase I clinical trial which is aim to evaluate the safety and tolerability of tumor-specific TCR-T cells. In this study, these TCR-T cells will be multiplied, or grown, in the laboratory.Subjects will received TCR-T cells infusions twice at day 0 and day 14, with the use of IL-2 for 5 consecutive days after every cell infusion.

Interventions

• Drug tumor-specific TCR-T cells
  On day 0 and day 14, 0.5-5x10\^9 TCR-T cells will be infused intravenously (IV) over 1 hour,patients may choose to receive more cell infusions if they benefit from the treatment.
• Drug Interleukin-2
  Aldesleukin 3,000,000 IU. IV.QD beginning within 24 hours of cell infusion and continuing for up to 5 days .

Primary outcome measures

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [Time frame: At least 45 days]

Secondary outcome measures (3)

• Disease Control Rate(DCR) [Time frame: one year]
• overall survival(OS) [Time frame: two year]
• progression-free survival(PFS) [Time frame: two year]

Eligibility criteria

Inclusion criteria

• Aged between 18 and 70 years old, regardless of gender;
• Diagnosed as solid tumors by histopathology, and the tumor lesions could be detected or evaluated;
• Be after standard treatment or who lack effective treatment programs;
• Patients and their families were willing to participate in the clinical trial and signed the informed consent;
• Physical status: ECOG score 0-1;
• Expected survival time > 3 months;
• HIV antibody negative;Hepatitis b surface antigen negative;Hepatitis c antibody negative;The results of blood routine and coagulation were roughly normal, lymphocyte >0.8×10\^9/L, hemoglobin >100g/L, and the pregnancy test of female patients with fertility potential was negative.
• Left ventricular ejection fraction 50% as indicated by cardiac ultrasound;Upper normal level of serum ALT/AST < 2.5 times;Serum creatinine 1.6mg/dl;Total bilirubin 1.5mg/dl, subject's total bilirubin < 3mg/dl except for Gilberts Syndrome;
• At least 4 weeks after the last systemic treatment, the patient's toxic and side effects must be restored to grade 1 or lower (except for alopecia or vitiligo).If the subject undergoes minor surgery within 3 weeks prior to enrollment, as long as all toxicity is recovered to level 1 or lower, the subject will meet the enrollment requirements.
• During the whole study period, patients can regularly visit the enrolled research institutions for relevant detection, evaluation and management;
• The patient is not allowed to use any anti-tumor drugs or treatments for 4 weeks prior to the infusion of TCR-T cells;
• Patients' tumor lesions can be obtained by surgery or puncture, and tumor infiltrating T cells can be successfully isolated from the obtained tumor tissue;
• T cells in patients' peripheral blood can effectively proliferate and expand by at least 10 times in the Pre-culture;
• The benefits of participating in the clinical trial outweigh the risks,which was evaluated by the researchers base on the status or condition of the patients.

Exclusion criteria

• Any form of primary immunodeficiency disease (such as severe combined immunodeficiency disease);
• Experiencing moderate to severe infection or possible opportunistic infection;
• Patients with a history of autoimmunity (e.g., SLE, psoriasis, etc.);
• Acute systemic infection, coagulation dysfunction or other serious cardiopulmonary diseases;
• Patients who have is suffering a large amount of glucocorticoid or other immunosuppressive agents within 4 weeks;
• Be allergic to any drug used in this study;
• Central nervous system metastases patients with clinically unstable or acute meningitis (except these clinically stable after treatment) Clinical stability needs to be met as follows: 4 weeks at least before the trial treatment, 1) no new brain lesion or no expanded of the original lesions confirmed by MRI); 2) no hormone therapy for at least 2 weeks; 3) neurological symptoms have returned to baseline;
• Pregnant and lactating women, as well as male and female patients who could not cooperate with contraception during the study period.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT03891706 · FI-FIT001-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗