Nasopharyngeal CarcinomaPhase 1NCT01462903
A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors
A Phase 1 study testing tumor infiltrating lymphocytes, IL-2 in people with Nasopharyngeal Carcinoma and Hepatocellular Carcinoma, run by Sun Yat-sen University at 2 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Nasopharyngeal Carcinoma, Hepatocellular Carcinoma, Breast Carcinoma
- What is being tested?
- tumor infiltrating lymphocytes, IL-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesChina
- Study dates
- Sep 2011to Dec 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Sun Yat-Sen University, Cancer Center
Guangzhou, Guangdong, 510060
Jiang Li, Ph.D., 86-20-87343174, lijiang@sysucc.org.cn
Yi-Xin Zeng, Ph.D.
- Recruiting
Sun Yat-Sen University, Cancer Center
Guangzhou, Guangdong, 510060
Jiang Li, Ph.D., 86-20-87343174, lijiang@sysucc.org.cn
Hai-Qiang Mai, Doctor, 86-20-87343360, maihq@sysucc.org.cn
About this study
Official title: 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.
Read the 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.
- Being tested
- tumor infiltrating lymphocytes, IL-2
- Keywords
- TIL, NPC, hepatocellular carcinoma, immunotherapy
- Medical subject headings
- Nasopharyngeal Carcinoma, Carcinoma, Hepatocellular, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tumor infiltrating lymphocytes, IL-2Biological
Also called TIL immunotherapy for cancers
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.
| Study group | Role | What they receive |
|---|---|---|
| Drug, T cell immunoterhapy | Experimental | Not described Receives: Biological: tumor infiltrating lymphocytes, IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
• 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.
Measured: {Time Frame: 12 months}
Secondary outcomes (1)
• 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.
Measured: [ Time Frame: 12 Months]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2011 (estimated)
- Study startSep 2011
- Primary completionNov 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiang Li, Sun Yat-sen University
- Investigators
- Yi-Xin Zeng, Ph.D., Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01462903
- Sponsor's protocol ID
- SenU-200902002-2
- Status last verified
- Nov 2014
- First submitted
- 29 Sep 2011
- Last updated
- 24 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21325070Dudley 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.
PubMed 20668005Besser 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.
PubMed 19342963Rosenberg 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.
PubMed 19304471
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors
- ClinicalTrials.gov ID
- NCT01462903
- Acronym / sponsor ID
- SenU-200902002-2
- Keywords
- TIL, NPC, hepatocellular carcinoma, immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Nov 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 1 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug, T cell immunoterhapy | Experimental | Biological: tumor infiltrating lymphocytes, IL-2 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tumor infiltrating lymphocytes, IL-2Also: TIL immunotherapy for cancersBiological: 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. | Biological | Drug, T cell immunoterhapy |
Primary outcome
• 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}
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.
1 secondary outcome
• 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]
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2014.
- Background: PubMed 21325070Weber 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.
- Background: PubMed 20668005Dudley 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.
- Background: PubMed 19342963Besser 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.
- Background: PubMed 19304471Rosenberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-Xin Zeng, Ph.D. principal investigator
Sun Yat-Sen University Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tumor infiltrating lymphocytes, IL-2 in people with Nasopharyngeal Carcinoma and Hepatocellular Carcinoma, run by Sun Yat-sen University at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jiang Li, Ph.D. (862087343174, lijiang@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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}). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01462903, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2014.