Nasopharyngeal CarcinomaPhase 1NATELLANCT00516087
LMP1- and LMP2-Specific CTLs to Patients With EBV-Positive NPC (NATELLA)
A Phase 1 study testing Genetically modified CTLs in people with Nasopharyngeal Carcinoma, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Patients have a type of cancer called nasopharyngeal carcinoma (NPC) which has either come back, not gone away or is at high risk for coming back after the best treatment we know for this disease. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Nasopharyngeal Carcinoma
- What is being tested?
- Genetically modified CTLs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2007to Jul 2013
- 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.
- Any patient with EBV positive NPC, in relapse or with primary resistant disease
- Patients with a life expectancy 6 weeks or greater
- Patients with bilirubin less than 2x normal, SGOT less than 3x normal, and Hgb more than 8.0.
- Patients with a Karnofsky score (age greater than/=16) of or Lansky score (age less than 16) of greater than/= 50
- Patients with a creatinine 2x normal for age or less
- Patients should have been off other investigational therapy for one month prior to entry in this study
- Patient, parent/guardian able to give informed consent
Who cannot join
- Severe intercurrent infection
- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Houston Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: Administration of LMP1- and LMP2-Specific Cytotoxic T-Lymphocytes to Patients With EBV-Positive Nasopharyngeal Carcinoma
Patients have a type of cancer called nasopharyngeal carcinoma (NPC) which has either come back, not gone away or is at high risk for coming back after the best treatment we know for this disease. We are inviting patients to participate in a research study using a new experimental therapy consisting of special immune system cells called LMP1- and LMP2-specific cytotoxic T lymphocytes (LMP1- and LMP2-CTLs).
Some patients with nasopharyngeal carcinoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage NPC, suggesting that it may play a role in causing the disease. 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 recognize and kill special parts of EBV infected cells can survive in blood and affect the tumor.
We have used this sort of therapy to treat a different type of cancer that occurs after bone marrow and solid organ transplant called post-transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. We grew T cells in the laboratory that recognized all 9 proteins and were able to prevent and treat post-transplant lymphoma. However nasopharyngeal carcinoma tumor cells only express 2 EBV proteins (LMP1 and LMP2) on their surfaces. In a previous study we made T cells that recognized all 9 proteins and gave them to patients with NPC. While some patients had a response, only a few patients had their cancer completely go away. We are now trying to find out if we can improve this treatment by growing and giving T cells where more of the cells will recognize two of the proteins expressed on NPC cells called LMP1 and LMP2. These special T cells are called LMP1- and LMP2-CTLs. These LMP1- and LMP2-CTLs are an investigational product not approved by the Food and Drug Administration.
Read the detailed description
Patients have an EBV-positive cancer. We had gotten permission to take blood from patients in the past, which was used to grow T cells in the laboratory. We first grew a special type of cell called dendritic cells to stimulate the T cells. We then put a specially produced human virus (adenovirus) that carries the LMP1 and LMP2 gene into the dendritic cells. These dendritic cells were then treated with radiation so they could not grow. They were then used to stimulate T cells. This stimulation trained the T cells to kill cells with LMP1 and LMP2 on their surface. We then grew these LMP1- and LMP2-specific CTLs by more stimulation with EBV infected cells (which we made from blood by infecting them with EBV in the laboratory and treated them with radiation so they would not grow). We also put the adenovirus that carries the LMP1 and LMP2 genes into these EBV infected cells so that we increase the amount of LMP1 and LMP2 that these cells have. Once we made sufficient numbers of T cells we tested them to make sure they kill cells with LMP1 and LMP2 on their surface. These cells are now ready to give to the patients if they agree to participate in this study.
If the patient agrees to this treatment they will get treated with two doses of LMP1-and LMP2-specific CTLs, each dose given 2 weeks apart. If the patient is a female of child-bearing potential, we will give them a pregnancy test within one week prior to the infusion. If the patient is pregnant, they will not be able to participate in the study. The study doctor will be notified.
The CTLs will be thawed and injected through a central line, if they have one, or through a vein in their arm over 1 to 10 minutes. They may receive a dose of Tylenol and Benadryl beforehand. We will then monitor the patient in clinic for 1 to 4 hours after the injection.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital. We will follow the patient in the clinic after the CTL injection and also follow results of their disease evaluations with the primary doctor.
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 teaspoonfuls) of blood will be taken. We will use this blood to look at the immune response in the blood to the cancer.
To learn if the injected T cells have anti-tumor activity, we will measure the size of the patient's tumor before the T-cell infusion and 8 weeks afterwards with routine imaging studies such as CT (computer tomogram), MRI (magnetic resonance imaging), or PET (Positron Emission Tomography). If the patient has stable disease or there is a reduction in the size of the tumor on imaging studies after the T-cell infusion, the patient can receive up to six additional doses of the T cells at 6 to 12 weeks intervals if they wish.
- Conditions
- Nasopharyngeal Carcinoma
- Being tested
- Genetically modified CTLs
- Keywords
- Nasopharyngeal Carcinoma
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetically modified CTLsBiological
LMP1- and LMP2-specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line.
Three different dosing schedules will be evaluated. Each patient will receive two injections, 14 days apart, according to the following dosing schedules:
Group One Day 0 2x10^7 cells/m2 Day 14 2x10^7 cells/m2
Group Two Day 0 2x10^7 cells/m2 Day 14 1x10^8 cells/m2
Group Three Day 0 1x10^8 cells/m2 Day 14 2x10^8 cells/m2
| Study group | Role | What they receive |
|---|---|---|
| Patients | Experimental | 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. Receives: Biological: Genetically modified CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
adverse events are being measured/assessed for the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in patients with EBV-positive nasopharyngeal carcinoma (NPC).
Measured: 12 months
Secondary outcomes (1)
Adverse events will be measured/obtained for information on the expansion, persistence and anti-tumor effects of autologous LMP1- and LMP2 specific CTL in patients with EBV-positive NPC.
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 posted14 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionDec 2012
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal CarcinomaStudies 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
- 23 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, Stephen Gottschalk, Baylor College of Medicine
- Investigators
- Stephen Gottschalk, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00516087
- Sponsor's protocol ID
- 21000-NATELLA
- Other IDs
- NATELLA
- Acronym
- NATELLA
- Status last verified
- Feb 2017
- First submitted
- 10 Aug 2007
- Last updated
- 7 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of LMP1- and LMP2-Specific Cytotoxic T-Lymphocytes to Patients With EBV-Positive Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT00516087
- Acronym / sponsor ID
- NATELLA / 21000-NATELLA
- Conditions
- Nasopharyngeal Carcinoma
- Keywords
- Nasopharyngeal Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 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 2007
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 14 Aug 2007 (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 carcinoma (NPC) which has either come back, not gone away or is at high risk for coming back after the best treatment we know for this disease. We are inviting patients to participate in a research study using a new experimental therapy consisting of special immune system cells called LMP1- and LMP2-specific cytotoxic T lymphocytes (LMP1- and LMP2-CTLs).
Some patients with nasopharyngeal carcinoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage NPC, suggesting that it may play a role in causing the disease. 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 recognize and kill special parts of EBV infected cells can survive in blood and affect the tumor.
We have used this sort of therapy to treat a different type of cancer that occurs after bone marrow and solid organ transplant called post-transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. We grew T cells in the laboratory that recognized all 9 proteins and were able to prevent and treat post-transplant lymphoma. However nasopharyngeal carcinoma tumor cells only express 2 EBV proteins (LMP1 and LMP2) on their surfaces. In a previous study we made T cells that recognized all 9 proteins and gave them to patients with NPC. While some patients had a response, only a few patients had their cancer completely go away. We are now trying to find out if we can improve this treatment by growing and giving T cells where more of the cells will recognize two of the proteins expressed on NPC cells called LMP1 and LMP2. These special T cells are called LMP1- and LMP2-CTLs. These LMP1- and LMP2-CTLs are an investigational product not approved by the Food and Drug Administration.
Detailed description
Patients have an EBV-positive cancer. We had gotten permission to take blood from patients in the past, which was used to grow T cells in the laboratory. We first grew a special type of cell called dendritic cells to stimulate the T cells. We then put a specially produced human virus (adenovirus) that carries the LMP1 and LMP2 gene into the dendritic cells. These dendritic cells were then treated with radiation so they could not grow. They were then used to stimulate T cells. This stimulation trained the T cells to kill cells with LMP1 and LMP2 on their surface. We then grew these LMP1- and LMP2-specific CTLs by more stimulation with EBV infected cells (which we made from blood by infecting them with EBV in the laboratory and treated them with radiation so they would not grow). We also put the adenovirus that carries the LMP1 and LMP2 genes into these EBV infected cells so that we increase the amount of LMP1 and LMP2 that these cells have. Once we made sufficient numbers of T cells we tested them to make sure they kill cells with LMP1 and LMP2 on their surface. These cells are now ready to give to the patients if they agree to participate in this study.
If the patient agrees to this treatment they will get treated with two doses of LMP1-and LMP2-specific CTLs, each dose given 2 weeks apart. If the patient is a female of child-bearing potential, we will give them a pregnancy test within one week prior to the infusion. If the patient is pregnant, they will not be able to participate in the study. The study doctor will be notified.
The CTLs will be thawed and injected through a central line, if they have one, or through a vein in their arm over 1 to 10 minutes. They may receive a dose of Tylenol and Benadryl beforehand. We will then monitor the patient in clinic for 1 to 4 hours after the injection.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital. We will follow the patient in the clinic after the CTL injection and also follow results of their disease evaluations with the primary doctor.
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 teaspoonfuls) of blood will be taken. We will use this blood to look at the immune response in the blood to the cancer.
To learn if the injected T cells have anti-tumor activity, we will measure the size of the patient's tumor before the T-cell infusion and 8 weeks afterwards with routine imaging studies such as CT (computer tomogram), MRI (magnetic resonance imaging), or PET (Positron Emission Tomography). If the patient has stable disease or there is a reduction in the size of the tumor on imaging studies after the T-cell infusion, the patient can receive up to six additional doses of the T cells at 6 to 12 weeks intervals if they wish.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients | Experimental | Biological: Genetically modified CTLsPatients 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 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.
- Any patient with EBV positive NPC, in relapse or with primary resistant disease
- Patients with a life expectancy 6 weeks or greater
- Patients with bilirubin less than 2x normal, SGOT less than 3x normal, and Hgb more than 8.0.
- Patients with a Karnofsky score (age greater than/=16) of or Lansky score (age less than 16) of greater than/= 50
Key exclusion criteria (2 listed)
- Severe intercurrent infection
- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.
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 |
|---|---|---|
| Genetically modified CTLsLMP1- and LMP2-specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. Three different dosing schedules will be evaluated. Each patient will receive two injections, 14 days apart, according to the following dosing schedules: Group One Day 0 2x10^7 cells/m2 Day 14 2x10^7 cells/m2 Group Two Day 0 2x10^7 cells/m2 Day 14 1x10^8 cells/m2 Group Three Day 0 1x10^8 cells/m2 Day 14 2x10^8 cells/m2 | Biological | Patients |
Primary outcome
adverse events are being measured/assessed for the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in patients with EBV-positive nasopharyngeal carcinoma (NPC).
Time frame: 12 months
1 secondary outcome
Adverse events will be measured/obtained for information on the expansion, persistence and anti-tumor effects of autologous LMP1- and LMP2 specific CTL in patients with EBV-positive NPC.
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 7 Feb 2017.
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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.
Stephen Gottschalk, 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 Genetically modified CTLs in people with Nasopharyngeal Carcinoma, 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 8 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 7 Feb 2017. 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?
adverse events are being measured/assessed for the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in patients with EBV-positive nasopharyngeal carcinoma (NPC). (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Feb 2017.