A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by Sun Yat-sen University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Jiang Li, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT01462903
First received: September 29, 2011
Last updated: November 3, 2011
Last verified: November 2011
  Purpose

Background: T cell based adoptive immunotherapy including CTL and TIL may stimulated the immune system and stop cancer cells from growing.

Objective: Phase I clinical trial to investigate the toxicity and immune response of therapy with autologous tumor infiltrating lymphocytes as adjuvant treatment for metastatic nasopharyngeal carcinoma and hepatocellular carcinoma after primary operation, radiotherapy and chemotherapy.

Methodology: Phase I clinical trial in patients with advanced nasopharyngeal carcinoma, hepatocellular carcinoma, breast cancer and other solid cancers. The investigators isolated lymphocytes from fresh tumor tissues, activated and expanded TILs in vitro; and infused the enough number (10e9 to 10e10) of TIL back patients.


Condition Intervention Phase
Nasopharyngeal Carcinoma
Hepatocellular Carcinoma
Breast Carcinoma
Biological: tumor infiltrating lymphocytes, IL-2
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors

Resource links provided by NLM:


Further study details as provided by Sun Yat-sen University:

Primary Outcome Measures:
  • • the safety and tolerability of autologous tumor infiltrating lymphocytes (TIL) in combination with Interleukin-2(IL-2) in patients with nasopharyngeal carcinoma (NPC). [ Time Frame: {Time Frame: 12 months} ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be assessed by looking at adverse events by standard NIH criteria and also by performing a Quality of Life assessment. Adverse events will be reported on the case report form. The problility of observing at least one subject experience an adverse event in a sample of 20 subjects is 0.99, if the probability of the event occurring is assumed to be 0.2. There will be 95% power to detect a change in the proportion of adverse events in the group from 0 before treatment to 0.2 after treatment.


Secondary Outcome Measures:
  • • immune efficacy and anti-tumor effects of autologous tumor infiltrating lymphocytes (TIL) in combination with Interleukin-2(IL-2) in patients with nasopharyngeal carcinoma (NPC). [ Time Frame: [ Time Frame: 12 Months] ] [ Designated as safety issue: Yes ]
    Treatment response will be measured by immune response including the frequency of EBV antigen-specific T cells and ELISPOT detection for IFNg, EBV DNA concentration and tumor size. These data will be examined for normality and transformed if required.


Estimated Enrollment: 20
Study Start Date: September 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug, T cell immunoterhapy Biological: tumor infiltrating lymphocytes, IL-2
Biological: Infusion of Tumor Infiltrating Lymphocytes (10e9-10e10 cells) by iv in 30 Minutes. Followed by daily sc injections of 2 MIE Interleukin-2 for two weeks.
Other Name: TIL immunotherapy for cancers

Detailed Description:

Tumor infiltrating lymphocytes were isolated from tumor tissues from tumor biopsy or operation. These TILs were cultured in human IL-2 medium for 2 to 3 weeks, and reactivated by OKT3, irradiated feeder cells from the PBMCs of healthy donors and LCL set from EBV-transformed normal B cells, and expanded in human IL-2 medium for another 15 days. 10e9 to 10e10 TILs were yielded. The phenotype, function and sterile were detected before these TILs infused patients. After accepting operation or first round of routine chemotherapy and radiotherapy, the patients were treated with autologous TILs 10e9-10e10 via intravenous in 30 min, q weekX2 weeks, and followed by two weeks with daily sc low-dose interleukine-2.

Patients will be evaluated for toxicity and immune response. Peripheral blood of patients using multimer analysis and/or ELISPOT assays. Additional, we will be able to determine anti-tumor effects from immunotherapy by evaluating the clinical response of patients with stable or progressive disease at the time of TILs infusion. Lastly, we will assess additional tumor markers in patients with relapsed/refractory disease by immunohistochemical staining of tumor sections from previous diagnostic or therapeutic biopsy samples to determine the incidence of additional tumor antigen targets that may be used in future studies.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with nasopharyngeal carcinoma in stage IVa or Ivb and patients with metastatic hepatocellular carcinoma were planned for tumor biopsy or primary surgeon
  • Age 18 to 70 years.
  • Willing to sign a durable power of attorney
  • Able to understand and sign the Informed Consent Document
  • Life expectancy of greater than three months
  • 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.
  • 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:

    • WBC (> 3000/mm(3)).
    • Platelet count greater than 100,000/mm.
    • Hemoglobin greater than 8.0 g/dl.
  • Chemistry:

    • Serum ALT/AST 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, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

Exclusion Criteria:

  • Previous treatment with IL-12.
  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • 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.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency 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 systemic steroid therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462903

Contacts
Contact: Jiang Li, Ph.D. 862087343174 lijiang@sysucc.org.cn
Contact: Yi-Xin Zeng, Ph.D. 862087343333 zengYX@sysucc.org.cn

Locations
China, Guangdong
Sun Yat-Sen University, Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Jiang Li, Ph.D.    86-20-87343174    lijiang@sysucc.org.cn   
Principal Investigator: Yi-Xin Zeng, Ph.D.         
Sub-Investigator: Jiang Li, Ph.D.         
Sun Yat-Sen University, Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Jiang Li, Ph.D.    86-20-87343174    lijiang@sysucc.org.cn   
Contact: Hai-Qiang Mai, Doctor    86-20-87343360    maihq@sysucc.org.cn   
Sub-Investigator: Hai-qiang Mai, Doctor         
Sponsors and Collaborators
Sun Yat-sen University
Investigators
Principal Investigator: Yi-Xin Zeng, Ph.D. Sun Yat-sen University
  More Information

Additional Information:
Publications:
Responsible Party: Jiang Li, Sun yat-sen University cancer center, biotherapy center, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT01462903     History of Changes
Other Study ID Numbers: SenU-200902002-2
Study First Received: September 29, 2011
Last Updated: November 3, 2011
Health Authority: China: Food and Drug Administration

Keywords provided by Sun Yat-sen University:
TIL
NPC
hepatocellular carcinoma
immunotherapy

Additional relevant MeSH terms:
Pharyngeal Neoplasms
Breast Neoplasms
Carcinoma
Carcinoma, Hepatocellular
Nasopharyngeal Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on August 20, 2014