A Study of Combination of Anti-PD1 Antibody-activated TILs and Chemotherapy in Colorectal Cancer

NCT ID: NCT03904537

Last Updated: 2019-04-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-19
• Study Completion Date: 2021-12-31

Brief Summary

This study was a phase I/II trial initiated by the investigator to evaluate the safety and tolerability of anti-programmed cell death protein 1 (anti-PD1) antibody-activated autologous tumor-infiltrating lymphocytes (TILs) combined with adjuvant chemotherapy in participants with stage III colon cancer. Twenty participants were enrolled and anti-PD1 antibody-activated TILs was infused into participants after the final of adjuvant chemotherapy to assess the safety and 3-year disease-free survival.

Detailed Description

Postoperative colon cancer participants received 4 to 8 cycles of XELOX regimen adjuvant chemotherapy and received anti-PD1 antibody-activated TILs on the day 15 of the final cycle of chemotherapy.

Fresh tumor tissues or sentinel lymph nodes were collected from participants with postoperative colon cancer, and the tumor tissues were digested with type IV collagenase at 37 °C for 2 to 4 hours. The cell pellet was washed, suspended in medium containing 10% AB serum, planted in a 24-well cell culture plate, and periodically changed according to the growth of the cells. After culturing for 2 to 3 weeks, TILs were co-stimulated with radioactively irradiated allogeneic peripheral blood mononuclear cells (PBMCs) and were expanded in 100 ml of Interleukin-2 (IL-2) medium in a cell culture flask. After rapid expansion for 15 days, the number of cells reached 0.1-1*10^10 cells. Before cell transfer, TILs were incubated with anti-PD-1 antibody, and a fraction of the TILs were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous TILs (0.1-1*10^10 cells) were transferred to participants via intravenous infusion.

Conditions

Colorectal Cancer Stage III

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PD1-TIL combined with chemotherapy

Participants would received anti-PD-1 antibody-activated TILs after the final adjuvant chemotherapy.

Group Type: EXPERIMENTAL

anti-PD-1 antibody-activated TILs

Intervention Type: BIOLOGICAL

Participants would received one dose anti-PD-1 antibody-activated TILs at the final cycle of XELOX regimen chemotherapy

Interventions

anti-PD-1 antibody-activated TILs

Participants would received one dose anti-PD-1 antibody-activated TILs at the final cycle of XELOX regimen chemotherapy

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Participants with stage III colorectal cancer and scheduled to receive adjuvant chemotherapy postoperation.
• Age 18 to 75 years.
• Willing to sign a durable power of attorney.
• Able to understand and sign the Informed Consent Document.
• Life expectancy of greater than six months.
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
• Adequate organ function.
• Serology:

Seronegative for HIV antibody. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

•Hematology: white blood cell count (> 3500/mm(3)). Platelet count greater than 100,000/mm(3). Hemoglobin greater than 9.0 g/dl.

•Chemistry: Serum Alanine aminotransferase/Aspartate aminotransferase less or equal to 2.5 times the upper limit of normal.

Serum creatinine less than or equal to 1.6 mg/dl. Total bilirubin less than or equal to 1.5 mg/dl.

Exclusion Criteria

• Previous treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) , anti-PD-1, and anti-Programmed death-ligand 1(PD-L1).
• Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Allogeneic tissue/organ transplantation.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• History of autoimmune disease
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• Concurrent antineoplastic therapies and systemic steroid therapy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Jianchuan Xia

Director of Biotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-Sen University, Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Jian-Chuan Xia, Ph.D.

Role: primary

xiajch@sysucc.org.cn

86-20-87345699

De-Sheng Weng, Ph.D.

Role: backup

wengds@sysucc.org.cn

86-20-87343404

Other Identifiers

B2018-148-02

Identifier Type: -

Identifier Source: org_study_id