臨床研究等提出・公開システム

A Phase 2 Study Using Short-term Cultured Anti-tumor Autologous Lymphocytes Following a Nonmyeloablative Conditioning and Low-dose Interleukin-2 Treatment in Patients with Recurrent, Metastatic, or Persistent Cervical Cancer.
(TILCC trial)

Study of Autologous Tumor Infiltrating Lymphocytes in the Treatment of Patients With Cervical Cancer (TIL Therapy for Advanced Cervical Cancer)

Matsumoto Morio

Takashi Iwata

Keio University School of Medicine

35 Shinanomachi,Shinjuku-ku,Tokyo

iwata@a8.keio.jp

Masaki Sugawara

Keio University School of Medicine

35 Shinanomachi,Shinjuku-ku,Tokyo

+81-3-5363-3819

masaki.sugawara@keio.jp

Interventional

single arm study

open(masking not used)

historical control

single assignment

treatment purpose

1. Pathologically confirmed cervical cancer.
2. Platinum-resistant recurrent or advanced cervical cancer.
3. Cervical cancer patient who is not amenable to curative treatment with surgery and/or radiation therapy.
4. Measurable metastatic cervical cancer with at least 1 lesion that is 1cm or more in size and is resectable for TIL generation during 1 to 2 weeks of admission.
5. Greater than or equal to 20 years of age and younger than or equal to 65 years of age.
6. Life expectancy of greater than 3 months from the registration date.
7. Clinical performance status of ECOG 0 or 1.
8. Normal values for basic laboratory values:
a) White Blood Cells (WBC): 2,000/microlitre or more.
b) Neutrophils: 1,000/microlitre or more.
c) Platelets: 75,000/microlitre or more.
d) Hemoglobin: 8.0g/dL or more.
e) AST:5.0xULN or less, and ALT:5.0xULN or less
f) Total Bilirubin :3xULN. or less
g) eGFRcreat : 50mL/min/1.73m2 or more
9. When systemic treatment such as chemotherapy is performed by the scheduled day for tumor resection, at least 4 weeks must have passed since the previous treatment, and the patient's toxicities must have recovered to grade 1 or less at the time the patient receives the preparative regimen.
10. Donor-derived peripheral blood mononuclear cells required for culture are stocked.
11. Patients of childbearing potential must be willing to practice an approved method of birth control starting at the time of informed consent and for 4 months after the completion of the study treatment regimen.
12. Able to understand and sign informed consent documents.

1. Patients who have been treated for nonmyeloablative or myeloablative conditioning.
2. Patients with symptomatic central nervous system infiltration due to brain metastases.
3. Women of child-bearing potential who are pregnant or breastfeeding.
4. Patients who are taking immunosuppressants or adrenocortical hormone. However, patients who have adrenal insufficiency caused by prior treatment with anti-PD-1 antibody or anti-CTLA4 antibody, and therefore, require steroid replacement for maintenance are exceptions.
5. Patients who cannot understand the contents of the explanatory document due to severe mental disorders.
6. Active major medical illnesses such as systemic infections, coagulation disorders, cardiovascular, respiratory, renal, or liver diseases, or type 2 diabetes without adequate glycemic control.
7. Patients who have other active primary malignancies (synchronous multiple cancer, or metachronous multiple cancer with a disease-free period of 5 years or less. However, intraepithelial or intramucosal cancer judged as completely cured by local treatment is an exception).
8. Patients with active autoimmune diseases.
9. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
10. Patients who have a left ventricular ejection fraction (LVEF) of less than 50%.
11. Patients with pleural effusion or pericardial effusion requiring treatment.
12. Patients whose FEV1% is 60% or less.
13. Carrier of HBV, HCV, HTLV-1, HIV. To be precise, patients with any of the following conditions: HBs Ag-positive; HBV-DNA positive (performed only if HBs or HBc antibody is positive); HCV-RNA positive (performed only if HCV antibody is positive);
HIV-Ab positive; HTLV-1 positive.
14. Patients who are judged inappropriate to be enrolled in this study by the doctor in charge.

Female

cervical cancer

After a tumor sample is resected from each cervical cancer patient and cultured ex vivo for the expansion of tumor infiltrating lymphocytes (TIL), the extracted autologous TIL are infused to each patient after NMA conditioning, followed by IL-2 administration.

C539

cervical cancer, TIL

Best overall response (BOR) rate based on Response Evaluation Criteria in Solid Tumours (RECIST) guideline (version 1.1).
Adverse events (type, frequency and severity) based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Duration of Response
Stable Period
Progression-Free Survival
Overall Survival

Recruiting

+81-3-5363-3503

Oct. 22, 2020