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

Primary Purpose

Nasopharyngeal Carcinoma, Hepatocellular Carcinoma, Breast Carcinoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

tumor infiltrating lymphocytes, IL-2

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring TIL, NPC, hepatocellular carcinoma, immunotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Sun Yat-Sen University, Cancer CenterRecruiting
Sun Yat-Sen University, Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Drug, T cell immunoterhapy

Arm Description

Outcomes

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).

Twenty of participants with adverse events as a measure of safety and tolerability according to standard NIH criteria including fever, mucositis, dermatitis, vomiting and hematologic toxicity leucopenia, neutropenia and lymphocytoponia etc. and 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).

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.

Full Information

NCT ID

NCT01462903

First Posted

September 29, 2011

Last Updated

November 21, 2014

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT01462903

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Unknown status

Study Start Date

September 2011 (undefined)

Primary Completion Date

November 2014 (Anticipated)

Study Completion Date

December 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasopharyngeal Carcinoma, Hepatocellular Carcinoma, Breast Carcinoma

Keywords

TIL, NPC, hepatocellular carcinoma, immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Drug, T cell immunoterhapy

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

tumor infiltrating lymphocytes, IL-2

Other Intervention Name(s)

TIL immunotherapy for cancers

Intervention Description

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.

Primary Outcome Measure Information:

Title

• the safety and tolerability of autologous tumor infiltrating lymphocytes (TIL) in combination with Interleukin-2(IL-2) in patients with nasopharyngeal carcinoma (NPC).

Description

Time Frame

{Time Frame: 12 months}

Secondary Outcome Measure Information:

Title

• 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).

Description

Time Frame

[ Time Frame: 12 Months]

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jiang Li, Ph.D.

Phone

862087343174

lijiang@sysucc.org.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Yi-Xin Zeng, Ph.D.

Phone

862087343333

zengYX@sysucc.org.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yi-Xin Zeng, Ph.D.

Organizational Affiliation

Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sun Yat-Sen University, Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiang Li, Ph.D.

Phone

86-20-87343174

lijiang@sysucc.org.cn

First Name & Middle Initial & Last Name & Degree

Yi-Xin Zeng, Ph.D.

First Name & Middle Initial & Last Name & Degree

Jiang Li, Ph.D.

Facility Name

Sun Yat-Sen University, Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiang Li, Ph.D.

Phone

86-20-87343174

lijiang@sysucc.org.cn

First Name & Middle Initial & Last Name & Degree

Hai-Qiang Mai, Doctor

Phone

86-20-87343360

maihq@sysucc.org.cn

First Name & Middle Initial & Last Name & Degree

Hai-qiang Mai, Doctor

12. IPD Sharing Statement

Citations:

PubMed Identifier

21325070

Citation

Weber J, Atkins M, Hwu P, Radvanyi L, Sznol M, Yee C; Immunotherapy Task Force of the NCI Investigational Drug Steering Committee. White paper on adoptive cell therapy for cancer with tumor-infiltrating lymphocytes: a report of the CTEP subcommittee on adoptive cell therapy. Clin Cancer Res. 2011 Apr 1;17(7):1664-73. doi: 10.1158/1078-0432.CCR-10-2272. Epub 2011 Feb 15.

Results Reference

background

PubMed Identifier

20668005

Citation

Dudley ME, Gross CA, Langhan MM, Garcia MR, Sherry RM, Yang JC, Phan GQ, Kammula US, Hughes MS, Citrin DE, Restifo NP, Wunderlich JR, Prieto PA, Hong JJ, Langan RC, Zlott DA, Morton KE, White DE, Laurencot CM, Rosenberg SA. CD8+ enriched "young" tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Clin Cancer Res. 2010 Dec 15;16(24):6122-31. doi: 10.1158/1078-0432.CCR-10-1297. Epub 2010 Jul 28.

Results Reference

background

PubMed Identifier

19342963

Citation

Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Schallmach E, Kubi A, Shalmon B, Hardan I, Catane R, Segal E, Markel G, Apter S, Nun AB, Kuchuk I, Shimoni A, Nagler A, Schachter J. Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. J Immunother. 2009 May;32(4):415-23. doi: 10.1097/CJI.0b013e31819c8bda.

Results Reference

background

PubMed Identifier

19304471

Citation

Rosenberg SA, Dudley ME. Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol. 2009 Apr;21(2):233-40. doi: 10.1016/j.coi.2009.03.002. Epub 2009 Mar 21.

Results Reference

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

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