Clinical trial NCT04766320: Study on TIL for the Treatment of r/r Gynecologic Tumors
Official title: A Clinical Safety and Efficacy Study on TIL for the Treatment of r/r Gynecologic Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gynecologic Cancer
Lead sponsor: Shanghai 10th People's Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Juncell Therapeutics
First posted: 2021-02-23
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with malignant refractory/relapsed gynecologic tumors. Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with fludarabine and cyclophosphamide.


Eligibility criteria: Inclusion Criteria:

1. Age: 18 years to 75 years;
2. Histologically diagnosed as primary/relapsed/metastasized malignant tumors;
3. Expected life-span more than 3 months;
4. Karnofsky≥60% or ECOG score 0-2;
5. Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
6. Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;
7. At least 1 evaluable tumor lesion;
8. Absolute count of white blood cells≥2.5×10\^9/L, absolute count of neutropils≥1.5×10\^9/L, platelet count≥100×10\^9, hemoglobin≥90 g/L;
9. Serum creatinine clearance 50mL/min or higher; creatinine≤1.5×ULN; ALT/AST less than three times that of normal group, ALT/AST of test subjects with liver metastasis less than five times that of normal group; bilirubin≤1.5×ULN;
10. Activated partial thromboplastin time (APTT) less than or equal to 1.5xULN; international normalized ratio (INR) less than or equal to 1.5xULN;
11. Enough venous accessibility, no absolute or relative contraindications to operation or biopsy;
12. Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion；
13. Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs;
14. Be able to understand and sign the informed consent document;
15. Be able to stick to follow-up visit plan and other requirements in the agreement.

Exclusion Criteria:

1. Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones);
2. Autoimmune diseases requiring immunomodulatory treatment;
3. Serum creatinine \>1.5×ULN; serum glutamic-oxalacetic transaminase (SGOT) greater than 5×ULN; bilirubin \>1.5×ULN;
4. Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;
5. Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.
6. Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;
7. Severe physical or mental diseases;
8. Blood culture positive or imaging proof;
9. Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
10. History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;
11. Having received immunotherapy and developed irAE level greater than Level 3;
12. Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);
13. Females in pregnancy or lactation;
14. Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Primary outcomes:
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 36 months
measure: Disease Control Rate (DCR）
timeFrame: Up to 36 months
measure: Duration of Response (DOR)
timeFrame: Up to 36 months
measure: Progression-Free Survival (PFS)
timeFrame: Up to 36 months
measure: Overall Survival (OS)
timeFrame: Up to 36 months
measure: Complete Response(CR)
timeFrame: Up to 36 months
measure: Partial Response (PR)
timeFrame: Up to 36 months
measure: Stable Disease (SD)
timeFrame: Up to 36 months
measure: Progressive Disease (PD)
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
Study officials:
References:
citation: Guo J, Luo N, Ai G, Yang W, Zhu J, Li C, Chen R, Zhang C, Liu S, Jin H, Cheng Z. Eradicating tumor in a recurrent cervical cancer patient with autologous tumor-infiltrating lymphocytes and a modified lymphodepleting regimen. J Immunother Cancer. 2022 Feb;10(2):e003887. doi: 10.1136/jitc-2021-003887.