Head and Neck CancerPhase 1NPCNCT00609219
T-Lymphocytes in Treating Patients With Epstein-Barr Virus-Positive Nasopharyngeal Cancer, NPC
A Phase 1 study testing autologous EBV specific CTLs in people with Head and Neck Cancer, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Patients have a type of cancer called nasopharyngeal cancer. This cancer has come back or not gone away or is at high risk for coming back after treatment (including the best treatment we know for nasopharyngeal cancer). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- autologous EBV specific CTLs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2001to Jun 2012
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients with NPC in first or subsequent relapse or with primary refractory disease or high risk (T3 or T4, or node positive disease) in whom the EBV genome or antigens have been demonstrated in tissue biopsies will be eligible for this trial. -Patients with a life expectancy >6 weeks
- Patients with a Karnofsky score of >/= 50
- No severe intercurrent infection.
- Patient, parent/guardian able to give informed consent.
- Patients with bilirubin <2x normal, SGOT <3x normal, and Hgb >8.0
- Patients with a creatinine <2x normal for age
- Patients should have been off other investigational therapy for one month prior to entry in this study.
Who cannot join
- -Patients with a life expectancy of <6 weeks. -Patients with a Karnofsky score of < 50. -Patients with a severe intercurrent infection. -Patient, parent/guardian unable to give informed consent. -Patients with a bilirubin >2x normal. SGOT >3x normal or abnormal prothrombin time. -Patients with a creatinine >2x normal for age -Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.
- Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigators discretion after approval by the CAGT Protocol Review Committee and the FDA reviewer.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Children's Hospital
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
About this study
Official title: Administration of EBV-Specific T-Lymphocytes to Patients With EBV-Positive Nasopharyngeal Carcinoma
Patients have a type of cancer called nasopharyngeal cancer. This cancer has come back or not gone away or is at high risk for coming back after treatment (including the best treatment we know for nasopharyngeal cancer). We are asking patients to volunteer to be in a research study using special immune system cells called EBV-specific cytotoxic T lymphocytes, a new experimental therapy.
Most patients with nasopharyngeal cancer show evidence of infection with the virus that causes infectious mononucleosis, Epstein Barr virus (EBV), before or at the time of their diagnosis of nasopharyngeal cancer. EBV is found in the cancer cells of most patients with nasopharyngeal cancer, suggesting that it may play a role in causing this cancer. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells (called T cells) that have been trained to kill EBV-infected cells can survive in the patient's blood and affect the tumor.
Read more
We have treated other patients with different EBV positive cancers and have had variable results. Some patients have had some response to the treatment. Some patients have been cured by the treatment. It is not possible for us to predict if this treatment will work for nasopharyngeal cancer.
The purposes of this study are to find the largest safe dose of EBV specific cytotoxic T cells, to learn what the side effects are, and to see whether this therapy might help patients with nasopharyngeal cancer.
Read the detailed description
We will first test a biopsy of the tumor (that has already been done) to see if your tumor cells are EBV positive. If the patient is eligible, we will then take 60-70 ml (12-14 teaspoons) of blood from them. We will use this blood to grow more of the T cells in the laboratory. We will first grow an EBV-infected cell line by infecting the blood with EBV virus. This line will then be irradiated so it cannot grow and used to stimulate the T cells. This stimulation will train the T cells to kill cells with EBV on their surface. We will then grow these EBV-specific CTLs by more stimulation with EBV infected cells and a growth factor called Interleukin 2. Next, we will test the T cells to make sure that they kill the EBV-infected cells. If the number of T cells produced is low, we may need to obtain additional blood samples to make these cells.
The cells (which are the patient's own T cells) will be injected into them over 10 minutes, after pretreatment with Tylenol and Benadryl. A total of two doses will be given two weeks apart. All of the Treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or the Methodist Hospital.
We will follow the patient in the clinic after the injections. To learn more about the way the T cells are working and how long they last in the body, an extra 10-60 mls (2-12 teaspoons) of blood will be taken before the infusion and 3-4 days after the infusion (this is optional). Up to 40 ml (8 teaspoons) of blood will also be drawn at 1, 2, 4 and 6 weeks post-infusion, and then at 3, 6, 9, and 12 months. The blood may be drawn from the patient's central line at the time of the regular blood tests. We will use this blood to look at the immune response to the patient's cancer. Over the course of the study, up to 29 tablespoons of blood will be drawn.
Patients will also have repeat scans at 8 weeks after the first injections. If these show stable or improving disease they may (if the patient wishs) receive up to 6 extra doses of cells. These would be given every 1-3 months. If the patient has additional injections of cells after the first two infusions, we will take extra blood tests before each infusion, at the end of each infusion, 3-4 days after each infusion (day optional depending on patient preference), and at 1 and 2 weeks after each infusion. We will also do an extra scan between 1 and 3 months after the last infusion. Follow up will then continue every 3 months and will continue until 12 months after the last infusion.
- Conditions
- Head and Neck Cancer
- Being tested
- autologous EBV specific CTLs
- Keywords
- recurrent nasopharyngeal cancer, stage II nasopharyngeal cancer, stage III nasopharyngeal cancer, stage IV nasopharyngeal cancer
- Medical subject headings
- Head and Neck Neoplasms, Nasopharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous EBV specific CTLsBiological
Also called EBV specific CTLs
30-40cc of peripheral blood will be used to generate EBV specific CTLs
Group One:
Day 0 - 2 x 10^7 cells/m2 Day 14 - 2 x 10^7 cells/m2
Group Two:
Day 0 - 2 x 10^7 cells/m2 Day 14 - 1 x 10^8 cells/m2
Group Three:
Day 0 - 1 x 10^8 cells/m2 Day 14 - 2 x 10^8 cells/m2
| Study group | Role | What they receive |
|---|---|---|
| EBV specific CTL | Experimental | autologous EBV specific CTLs Receives: Biological: autologous EBV specific CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of two IV injections of autologously derived Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs)
Patients will be enrolled at the first dose level and followed for six weeks after the second dose (which will constitute a course) for evaluation of any critical toxicity
Measured: 6 weeks
Secondary outcomes (1)
the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2008 (estimated)
- Study startAug 2001
- Primary completionOct 2007
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Helen Heslop, Baylor College of Medicine
- Investigators
- Helen E. Heslop, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00609219
- Sponsor's protocol ID
- H-9935-NPC
- Other IDs
- NPC
- Acronym
- NPC
- Status last verified
- Oct 2012
- First submitted
- 2 Feb 2008
- Last updated
- 10 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Louis CU, Straathof K, Bollard CM, Ennamuri S, Gerken C, Lopez TT, Huls MH, Sheehan A, Wu MF, Liu H, Gee A, Brenner MK, Rooney CM, Heslop HE, Gottschalk S. Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother. 2010 Nov-Dec;33(9):983-90. doi: 10.1097/CJI.0b013e3181f3cbf4.
PubMed 20948438Straathof KC, Bollard CM, Popat U, Huls MH, Lopez T, Morriss MC, Gresik MV, Gee AP, Russell HV, Brenner MK, Rooney CM, Heslop HE. Treatment of nasopharyngeal carcinoma with Epstein-Barr virus--specific T lymphocytes. Blood. 2005 Mar 1;105(5):1898-904. doi: 10.1182/blood-2004-07-2975. Epub 2004 Nov 12.
PubMed 15542583
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of EBV-Specific T-Lymphocytes to Patients With EBV-Positive Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT00609219
- Acronym / sponsor ID
- NPC / H-9935-NPC
- Conditions
- Head and Neck Cancer
- Keywords
- recurrent nasopharyngeal cancer, stage II nasopharyngeal cancer, stage III nasopharyngeal cancer, stage IV nasopharyngeal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Aug 2001
- Primary completion
- Oct 2007 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 6 Feb 2008 (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.
Patients have a type of cancer called nasopharyngeal cancer. This cancer has come back or not gone away or is at high risk for coming back after treatment (including the best treatment we know for nasopharyngeal cancer). We are asking patients to volunteer to be in a research study using special immune system cells called EBV-specific cytotoxic T lymphocytes, a new experimental therapy.
Most patients with nasopharyngeal cancer show evidence of infection with the virus that causes infectious mononucleosis, Epstein Barr virus (EBV), before or at the time of their diagnosis of nasopharyngeal cancer. EBV is found in the cancer cells of most patients with nasopharyngeal cancer, suggesting that it may play a role in causing this cancer. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells (called T cells) that have been trained to kill EBV-infected cells can survive in the patient's blood and affect the tumor.
We have treated other patients with different EBV positive cancers and have had variable results. Some patients have had some response to the treatment. Some patients have been cured by the treatment. It is not possible for us to predict if this treatment will work for nasopharyngeal cancer.
The purposes of this study are to find the largest safe dose of EBV specific cytotoxic T cells, to learn what the side effects are, and to see whether this therapy might help patients with nasopharyngeal cancer.
Detailed description
We will first test a biopsy of the tumor (that has already been done) to see if your tumor cells are EBV positive. If the patient is eligible, we will then take 60-70 ml (12-14 teaspoons) of blood from them. We will use this blood to grow more of the T cells in the laboratory. We will first grow an EBV-infected cell line by infecting the blood with EBV virus. This line will then be irradiated so it cannot grow and used to stimulate the T cells. This stimulation will train the T cells to kill cells with EBV on their surface. We will then grow these EBV-specific CTLs by more stimulation with EBV infected cells and a growth factor called Interleukin 2. Next, we will test the T cells to make sure that they kill the EBV-infected cells. If the number of T cells produced is low, we may need to obtain additional blood samples to make these cells.
The cells (which are the patient's own T cells) will be injected into them over 10 minutes, after pretreatment with Tylenol and Benadryl. A total of two doses will be given two weeks apart. All of the Treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or the Methodist Hospital.
We will follow the patient in the clinic after the injections. To learn more about the way the T cells are working and how long they last in the body, an extra 10-60 mls (2-12 teaspoons) of blood will be taken before the infusion and 3-4 days after the infusion (this is optional). Up to 40 ml (8 teaspoons) of blood will also be drawn at 1, 2, 4 and 6 weeks post-infusion, and then at 3, 6, 9, and 12 months. The blood may be drawn from the patient's central line at the time of the regular blood tests. We will use this blood to look at the immune response to the patient's cancer. Over the course of the study, up to 29 tablespoons of blood will be drawn.
Patients will also have repeat scans at 8 weeks after the first injections. If these show stable or improving disease they may (if the patient wishs) receive up to 6 extra doses of cells. These would be given every 1-3 months. If the patient has additional injections of cells after the first two infusions, we will take extra blood tests before each infusion, at the end of each infusion, 3-4 days after each infusion (day optional depending on patient preference), and at 1 and 2 weeks after each infusion. We will also do an extra scan between 1 and 3 months after the last infusion. Follow up will then continue every 3 months and will continue until 12 months after the last infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EBV specific CTL | Experimental | Biological: autologous EBV specific CTLsautologous EBV specific CTLs |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- All patients with NPC in first or subsequent relapse or with primary refractory disease or high risk (T3 or T4, or node positive disease) in whom the EBV genome or antigens have been demonstrated in tissue biopsies will be eligible for this trial. -Patients with a life expectancy >6 weeks
- Patients with a Karnofsky score of >/= 50
- No severe intercurrent infection.
- Patient, parent/guardian able to give informed consent.
- Patients with bilirubin <2x normal, SGOT <3x normal, and Hgb >8.0
Key exclusion criteria (2 listed)
- -Patients with a life expectancy of <6 weeks. -Patients with a Karnofsky score of < 50. -Patients with a severe intercurrent infection. -Patient, parent/guardian unable to give informed consent. -Patients with a bilirubin >2x normal. SGOT >3x normal or abnormal prothrombin time. -Patients with a creatinine >2x normal for age -Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.
- Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigators discretion after approval by the CAGT Protocol Review Committee and the FDA reviewer.
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 |
|---|---|---|
| autologous EBV specific CTLsAlso: EBV specific CTLs30-40cc of peripheral blood will be used to generate EBV specific CTLs Group One: Day 0 - 2 x 10^7 cells/m2 Day 14 - 2 x 10^7 cells/m2 Group Two: Day 0 - 2 x 10^7 cells/m2 Day 14 - 1 x 10^8 cells/m2 Group Three: Day 0 - 1 x 10^8 cells/m2 Day 14 - 2 x 10^8 cells/m2 | Biological | EBV specific CTL |
Primary outcome
Safety of two IV injections of autologously derived Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs)
Time frame: 6 weeks
Patients will be enrolled at the first dose level and followed for six weeks after the second dose (which will constitute a course) for evaluation of any critical toxicity
1 secondary outcome
the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines.
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2012.
- Background: PubMed 20948438Louis CU, Straathof K, Bollard CM, Ennamuri S, Gerken C, Lopez TT, Huls MH, Sheehan A, Wu MF, Liu H, Gee A, Brenner MK, Rooney CM, Heslop HE, Gottschalk S. Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother. 2010 Nov-Dec;33(9):983-90. doi: 10.1097/CJI.0b013e3181f3cbf4.
- Results publication: PubMed 15542583Straathof KC, Bollard CM, Popat U, Huls MH, Lopez T, Morriss MC, Gresik MV, Gee AP, Russell HV, Brenner MK, Rooney CM, Heslop HE. Treatment of nasopharyngeal carcinoma with Epstein-Barr virus--specific T lymphocytes. Blood. 2005 Mar 1;105(5):1898-904. doi: 10.1182/blood-2004-07-2975. Epub 2004 Nov 12.
Related trials for Head and Neck Cancer
Active, not recruitingPhase 2
Study of Proton Versus Photon Beam Radiotherapy in the Treatment of Head and Neck Cancer
Head and Neck Cancer
Active, not recruitingObservational study
EValuating the Safety Of De-escaLated Head and Neck Irradiation in HPV positivE Oropharynx Cancer in Non-smokers/Minimal Smokers
Oropharyngeal Cancer
Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Breast Cancer, Ovarian Cancer
RecruitingPhase 1
Autologous CAR-T Cells Targeting CSPG4 in Relapsed/Refractory HNSCC
Head and Neck Cancer, Relapse
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
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.
Helen E. Heslop, MD principal investigator
Baylor College of Medicine
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 autologous EBV specific CTLs in people with Head and Neck Cancer, run by Baylor College of Medicine at 2 sites in United States.
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 7 inclusion and 2 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: finished, as of the sponsor's last update on 10 Oct 2012. 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 United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of two IV injections of autologously derived Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs) (time frame: 6 weeks). 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 NCT00609219, which also lists 2 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 10 Oct 2012; AzTrials last refreshed its copy on 6 Nov 2026.