Immunotherapy for the Treatment of Advanced Solid Tumor

January 31, 2024 updated by: Wang Hui,MD, Tongji Hospital

Immunotherapy Using Precision T Cells Specific to Personalized Neo-antigen for the Treatment of Advanced Solid Tumor

The purpose of this study is to evaluate the safety, side effects and benefits of autologous tumor infiltrating lymphocytes (TIL) specific to personalized Neo-antigens in the treatment of patients with recurrent, metastatic and advanced solid tumors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Adoptive cell transfer therapy that utilizes an autologous TIL manufacturing progress is originally developed by the NCI for the treatment of patients with recurrent, metastatic cervical cancer and liver cancer. TILs specific to personalized neo-antigens will be expended in vitro and given back to the patients through vein. A total of 20 patients will be enrolled in the single-arm, open label, interventional study.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Recruiting
        • Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology
        • Contact:
          • Wang
        • Principal Investigator:
          • Zhiyong Huang

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

To be eligible for the study, patients must meet ALL of the following criteria prior to enrollment in the study:

  1. Must be ≥ 18 years of age at the time of consent.
  2. Must have recurrent, metastatic, or persistent carcinoma that is not amenable to curative treatment with surgery and/or radiation therapy and for which no other therapies are expected to have significant benefit, in the opinion of the Investigator.
  3. Must have at least 1 lesion that is resectable for TIL generation. The resected TIL generating lesion(s) should yield at least 1.5 cm in diameter post-resection of tumor tissue. Following resection for TIL generation, must have a remaining measurable target lesion as defined by RECIST v1.1.
  4. Patients must have progressive disease while receiving or after the completion of the most recent prior treatment.
  5. Any prior therapy directed at the malignant tumor must be discontinued at least 28 days prior to tumor resection. Radiation therapy may have been received up to 28 days prior to tumor resection for lesions not expected to be used for TIL generation or target lesions.
  6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Patients must be seronegative for the human immunodeficiency virus (HIV).
  8. Patients with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or hepatitis C virus (anti-HCV) indicating acute or chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment.

  9. Hematology:

    Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim;White blood cell (WBC) greater than or equal to 3000/mm(3);Platelet count greater than or equal too 100,000/mm(3);Hemoglobin greater than 8.0 g/dl.

  10. Chemistry:

    Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to to 2.5 times the upper limit of normal. Serum creatinine less than or equal to to 1.6 mg/dl.Total bilirubin less that or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

  11. Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.

Exclusion Criteria:

  1. Patients who have received an organ allograft or prior cell transfer therapy.
  2. Patients who are on a systemic steroid therapy > 10 mg of prednisone daily or other steroid equivalent.
  3. Patients who currently have prior therapy-related toxicities greater than Grade 1 according to NCI-CTCAE v4.03; except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment/resection.
  4. Patients who have a contraindication to or history of hypersensitivity reaction to any component or excipients of the TIL therapy and the other study drugs.
  5. Patients with active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory, or immune system.
  6. Patients with symptomatic and/or untreated brain metastases (of any size and any number).
  7. Patients who have any form of primary or acquired immunodeficiency syndrome, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS).
  8. Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis.

  9. Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association (NYHA) Class 2 or higher.

    Patients who have a forced expiratory volume in 1 second (FEV1) of less than or equal to 60% of predicted normal.

  10. Patients who have received a live or attenuated vaccine within 28 days of the NMA-LD regimen.
  11. Patients whose cancer requires immediate treatment or who would otherwise suffer a disadvantage by participating in this study.
  12. Patients who have received prior treatment with immunotherapy (eg, anti-PD-1 anti-PD-L1, or anti-CTLA4 antibodies)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TIL,IL-2,Cyclophosphamide,Fludarabine

Biological: TIL On day 0, cells will be infused intravenously over 20 to 30 minutes (one to four days after the last dose of fludarabine).

Drug: Aldesleukin 125,000 IU/kg IV/day (based on total body weight) beginning within 24 hours of cell infusion and continuing for up to 2 weeks) Drug: Cyclophosphamide On day -7 and day -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.

Drug: Fludarabine Days -5 to -1: Fludarabine 25 mg /m2/day IVPB daily over 30 minutes for 5 days.
Biological: TIL
On day 0, cells will be infused intravenously over 20 to 30 minutes (one to four days after the last dose of fludarabine)
Drug: Cyclophosphamide
On day -7 and day -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
Other Names:
  • CTX
Drug: Aldesleukin
IL-2 125,000 IU/kg/day IV (based on total body weight) beginning within 24 hours of cell infusion and continuing for up to 2 weeks
Other Names:
  • IL-2
Drug: Fludarabine
Days -5 to -1: Fludarabine 25 mg /m2/day IVPB daily over 30 minutes for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Responce Rate [Time Frame: 24 months after cell infusion]
Time Frame: 24 months after cell infusion
The Objective Responce Rate of patients received immunotherapy are accesed by the Response Criteria in Solid Tumors (RECIST) v1.0.
24 months after cell infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Event
Time Frame: up to 24 months
Aggregate of all adverse events, as well as their frequency and severity are accessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.03).
up to 24 months
Disease Control Rate
Time Frame: up to 24 months
Disease control rate (DCR) as measured by RECIST 1.1 criteria.
up to 24 months
Duration of Response
Time Frame: up to 24 months
Duration of response (DOR) as measured by RECIST 1.1 criteria .
up to 24 months
Progression-Free Survival
Time Frame: up to 24 months
PFS will be summarized using Kaplan-Meier estimates.
up to 24 months
Overall Survival
Time Frame: up to 24 months
The overall survival of all patients entering the study will be monitored.
up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tongji Hospital

Investigators

  • Study Chair: Hui Wang, MD, Tongji Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2020

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

September 3, 2018

First Submitted That Met QC Criteria

September 3, 2018

First Posted (Actual)

September 5, 2018

Study Record Updates

Last Update Posted (Actual)

February 2, 2024

Last Update Submitted That Met QC Criteria

January 31, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018TNB-V01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Solid Tumor

Clinical Trials on TIL

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe