Using tumor infiltrating lymphocytes to treat recurrent gynecologic cancers

A Clinical Safety and Efficacy Study on TIL for the Treatment of r/r Gynecologic Tumors

This study is testing a new treatment using immune cells from tumors to see if it can help women with hard-to-treat gynecologic cancers feel better when other treatments haven't worked.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Shanghai 10th People's Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Prednisone, cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT04766320 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy for patients with refractory or relapsed gynecologic tumors. The approach involves expanding autologous TILs from tumor resections or biopsies and infusing them intravenously after a non-myeloablative lymphodepletion treatment with fludarabine and cyclophosphamide. The goal is to assess how well this treatment can help patients who have not responded to standard therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed malignant gynecologic tumors who have failed standard treatments.

Not a fit: Patients with non-malignant tumors or those who are not eligible for biopsy or resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat gynecologic cancers.

How similar studies have performed: Other studies using TIL therapy have shown promising results in various cancers, suggesting potential success for this approach in gynecologic tumors.

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.

Where this trial is running

Shanghai, Shanghai

• Shanghai Tenth People's Hospital — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Jing Guo, PHd

Conditions Gynecologic Cancer