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

September 29, 2011
November 3, 2011
September 2011
December 2013   (final data collection date for primary outcome measure)
• 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.
• To determine the safety 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 ]
Administration and Monitoring Patients will be evaluated in the clinic and eligibility and informed consent obtained. Patients will be monitored for clinical toxicity by standard NIH criteria. A time period of 4 weeks will constitute the time for clinical safety monitoring.
Complete list of historical versions of study NCT01462903 on ClinicalTrials.gov Archive Site
• 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.
• To obtain information on the immune response 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 ]
The investigators will analyze immunological parameters by multimer studies in patients such as ELISPOT assay. The levels of EBV DNA in peripheral blood before and following infusion will be compared. Imaging studies include diagnostic imaging to document measurable disease and response to therapy (MRI, CT scans or PET scans) pre-infusion of TIL.
Not Provided
Not Provided
 
A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors
A Phase I Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Nasopharyngeal Carcinoma
  • Hepatocellular Carcinoma
  • Breast Carcinoma
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
Experimental: Drug, T cell immunoterhapy
Intervention: Biological: tumor infiltrating lymphocytes, IL-2

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
December 2013
December 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 70 Years
No
Contact: Jiang Li, Ph.D. 862087343174 lijiang@sysucc.org.cn
Contact: Yi-Xin Zeng, Ph.D. 862087343333 zengYX@sysucc.org.cn
China
 
NCT01462903
SenU-200902002-2
Yes
Jiang Li, Sun Yat-sen University
Sun Yat-sen University
Not Provided
Principal Investigator: Yi-Xin Zeng, Ph.D. Sun Yat-sen University
Sun Yat-sen University
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP