Epstein-Barr Virus-Related Hodgkin LymphomaPhase 1NCT00058617
Epstein Barr Virus (EBV) Specific Cytotoxic T-Cells, Relapsed Lymphoma, ANGEL
A Phase 1 study testing Injection of EBV Specific CTLs in people with Epstein-Barr Virus-Related Hodgkin Lymphoma and Epstein-Barr Virus-Related Non-Hodgkin Lymphoma, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Patients have a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma which has come back or not gone away after treatment, including the best treatment known for relapsed Lymphoma. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Epstein-Barr Virus-Related Hodgkin Lymphoma, Epstein-Barr Virus-Related Non-Hodgkin Lymphoma, EBV Positive Plasma Cell Neoplasm
- What is being tested?
- Injection of EBV Specific CTLs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 1996to Jul 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Any patient with EBV positive Hodgkin disease or non-Hodgkin Lymphoma, or plasma cell neoplasms in second relapse regardless of age or sex, in first relapse or with primary disease or in first remission if immunosuppressive chemotherapy contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richters transformation of CLL.
- Life expectancy of greater than 6 weeks.
- No severe intercurrent infection
- Patient, parent/guardian able to give informed consent
- Bilirubin <2x normal,
- SGOT <3x normal,
Show all 10Show fewer
- Hgb greater than 8.0 g/L
- Creatinine <2x normal for age
- Must have been off other investigational therapy for one month prior to entry in this study.
- Karnofsky score of greater than or equal to 50.
Who cannot join
- Patient with an EBV positive NHL secondary to an acquired immunodeficiency.
- Patients who are HIV positive
- Patient, parent/guardian unable to give informed consent
- Patients with a Karnofsky score of < 50.
- Patients with a life expectancy of <6 weeks
- Patients with a bilirubin greater than 2x normal. SGOT greater than 3x normal
Show all 9Show fewer
- Patients with a creatinine greater than 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 investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA reviewer.
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 Neomycin Resistance Gene Marked EBV Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma
Patients have a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma which has come back or not gone away after treatment, including the best treatment known for relapsed Lymphoma.
Patients are being asked to volunteer to be in a research study using Epstein Barr virus specific cytotoxic T lymphocytes, a new experimental therapy. This therapy has never been used in patients with Hodgkin disease or this type of non-Hodgkin Lymphoma but it has been used successfully in children with other types of blood cancer caused by EBV after bone marrow transplantation. Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus before or at the time of their diagnosis of the Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. Investigators want to see if it's possible to grow special white blood cells, called T cells, that have been trained to kill EBV infected cells.
Purpose The purpose of this study is 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 Hodgkin disease and non-Hodgkin Lymphoma.
Read the detailed description
The investigators will take 60-70 ml (12 teaspoonfuls) of blood from the patient to make a B cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV called B95-8. The investigators will then use this EBV infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood. This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. The investigators will then test the T cells to make sure that they kill the EBV infected cells and not normal cells and freeze them.
Patients will be entered into one of three different dosing schedules being evaluated. Three to six patients will be evaluated on each dosing schedule. Escalation will continue until irreversible or life threatening side effects considered to be related to the T cells are seen.
The cells will then be thawed and injected into the patients' vein over 10 minutes, after pretreatment with Tylenol and Benadryl. Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration. Initially, two doses of T cells will be given two weeks apart. If after the second infusion there is a reduction in the size of the patient's lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up to six additional doses of the T cells. All of the treatments will be given at Texas Children's Hospital or the Methodist Hospital.
Patients will be followed 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 40 mls (8 teaspoonfuls) of blood will be taken before each infusion and then 24 hours after each infusion, 3-4 days after each infusion and at 1, 2, 4, and 6 weeks post infusion and then at 3, 6, 9 and 12 months post infusion. The blood may be drawn from the central line at the time of regular blood tests. This blood will be used to test for the frequency and activity of EBV specific T cells. A total of at least 122 teaspoons (approximately 40 tablespoons) of blood will be collected during participation in this study.
If the patient decide to withdraw at any time during the study both samples and data collected during participation will be maintained.
- Conditions
- Epstein-Barr Virus-Related Hodgkin Lymphoma, Epstein-Barr Virus-Related Non-Hodgkin Lymphoma, EBV Positive Plasma Cell Neoplasm
- Being tested
- Injection of EBV Specific CTLs
- Keywords
- EBV Positive Hodgkin's Lymphoma, EBV Positive Non-Hodgkin's Lymphoma, EBV Specific Cytotoxic T-Lymphocytes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection of EBV Specific CTLsBiological
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 2x 10^8 cells/m2
If patients with active disease have stable disease or a partial response by the RECIST criteria at their 8 week or subsequent evaluations they are eligible to receive up to 6 additional doses of CTLs at monthly intervals-each of which will consist of the same cell number as their second injection. Patients will not be able to receive additional doses until the initial safety profile is completed at 6 weeks following the second infusion.
| Study group | Role | What they receive |
|---|---|---|
| Injection of EBV Specific CTLs | Experimental | Subjects will receive autologous EBV Specific CTLs. Patients that agree will recieve CTLs that have been marked with the neomycin resistance gene. Receives: Biological: Injection of EBV Specific CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of two IV injections of auto EBV specific CTLs will be determined through adverse event measurement. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector.
Three 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. The toxicity will be evaluated as per the NCI Common Toxicity criteria version 2.0.Any toxicity scored as Grade 3 or 4 according to this criteria will be classified as an adverse event. If no toxicity is observed in the first three patients then we will enroll another three patients at the next dose level. However, if toxicity is observed in no more than one out of the three patients then three more patients will be enrolled at the same dose level. Now if the toxicity is observed in no more than one out of the six patients then we will advance to the next dose level and enroll three new patients. If toxicity is observed in two or more patients out of six then the dose limiting toxicity (DLT) has been exceeded and the previous dose level will be considered as the maximum tolerated dose (MTD) level.
Measured: 6 weeks
To determine the feasibility of generating EBV specific cytotoxic T cell lines from patients with active EBV positive Lymphoma including Hodgkin Disease (HD) or Non-Hodgkin Lymphoma (NHL).
Measured: 6 weeks
To determine the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines.
During the course of the study the survival, immunological efficacy and anti-tumor activity of neomycin resistance gene marked EBV specific cytotoxic T-lymphocyte lines will also be studied. In order to gain reasonable insight into the anti-tumor activity and late toxicity the patients will be followed for a total of twelve weeks.In the present case, the chances of observing any late toxicity should be if anything lower, as in this case the CTLs will be derived autologously.
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2003 (estimated)
- Study startJan 1996
- Primary completionAug 2011
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epstein-Barr Virus-Related Hodgkin LymphomaStudies 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
- 13 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
- NCT00058617
- Sponsor's protocol ID
- 6423-ANGEL
- Other IDs
- ANGEL
- Status last verified
- Feb 2017
- First submitted
- 8 Apr 2003
- Last updated
- 15 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 15 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Neomycin Resistance Gene Marked EBV Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma
- ClinicalTrials.gov ID
- NCT00058617
- Acronym / sponsor ID
- 6423-ANGEL
- Conditions
- Epstein-Barr Virus-Related Hodgkin Lymphoma, Epstein-Barr Virus-Related Non-Hodgkin Lymphoma, EBV Positive Plasma Cell Neoplasm
- Keywords
- EBV Positive Hodgkin's Lymphoma, EBV Positive Non-Hodgkin's Lymphoma, EBV Specific Cytotoxic T-Lymphocytes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 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
- Jan 1996
- Primary completion
- Aug 2011 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 9 Apr 2003 (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 lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma which has come back or not gone away after treatment, including the best treatment known for relapsed Lymphoma.
Patients are being asked to volunteer to be in a research study using Epstein Barr virus specific cytotoxic T lymphocytes, a new experimental therapy. This therapy has never been used in patients with Hodgkin disease or this type of non-Hodgkin Lymphoma but it has been used successfully in children with other types of blood cancer caused by EBV after bone marrow transplantation. Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus before or at the time of their diagnosis of the Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. Investigators want to see if it's possible to grow special white blood cells, called T cells, that have been trained to kill EBV infected cells.
Purpose The purpose of this study is 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 Hodgkin disease and non-Hodgkin Lymphoma.
Detailed description
The investigators will take 60-70 ml (12 teaspoonfuls) of blood from the patient to make a B cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV called B95-8. The investigators will then use this EBV infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood. This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. The investigators will then test the T cells to make sure that they kill the EBV infected cells and not normal cells and freeze them.
Patients will be entered into one of three different dosing schedules being evaluated. Three to six patients will be evaluated on each dosing schedule. Escalation will continue until irreversible or life threatening side effects considered to be related to the T cells are seen.
The cells will then be thawed and injected into the patients' vein over 10 minutes, after pretreatment with Tylenol and Benadryl. Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration. Initially, two doses of T cells will be given two weeks apart. If after the second infusion there is a reduction in the size of the patient's lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up to six additional doses of the T cells. All of the treatments will be given at Texas Children's Hospital or the Methodist Hospital.
Patients will be followed 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 40 mls (8 teaspoonfuls) of blood will be taken before each infusion and then 24 hours after each infusion, 3-4 days after each infusion and at 1, 2, 4, and 6 weeks post infusion and then at 3, 6, 9 and 12 months post infusion. The blood may be drawn from the central line at the time of regular blood tests. This blood will be used to test for the frequency and activity of EBV specific T cells. A total of at least 122 teaspoons (approximately 40 tablespoons) of blood will be collected during participation in this study.
If the patient decide to withdraw at any time during the study both samples and data collected during participation will be maintained.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Injection of EBV Specific CTLs | Experimental | Biological: Injection of EBV Specific CTLsSubjects will receive autologous EBV Specific CTLs. Patients that agree will recieve CTLs that have been marked with the neomycin resistance gene. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Any patient with EBV positive Hodgkin disease or non-Hodgkin Lymphoma, or plasma cell neoplasms in second relapse regardless of age or sex, in first relapse or with primary disease or in first remission if immunosuppressive chemotherapy contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richters transformation of CLL.
- Life expectancy of greater than 6 weeks.
- No severe intercurrent infection
- Patient, parent/guardian able to give informed consent
- Bilirubin <2x normal,
Key exclusion criteria (9 listed)
- Patient with an EBV positive NHL secondary to an acquired immunodeficiency.
- Patients who are HIV positive
- Patient, parent/guardian unable to give informed consent
- Patients with a Karnofsky score of < 50.
- Patients with a life expectancy of <6 weeks
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 |
|---|---|---|
| Injection of EBV Specific CTLsEach 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 2x 10^8 cells/m2 If patients with active disease have stable disease or a partial response by the RECIST criteria at their 8 week or subsequent evaluations they are eligible to receive up to 6 additional doses of CTLs at monthly intervals-each of which will consist of the same cell number as their second injection. Patients will not be able to receive additional doses until the initial safety profile is completed at 6 weeks following the second infusion. | Biological | Injection of EBV Specific CTLs |
Primary outcome
The safety of two IV injections of auto EBV specific CTLs will be determined through adverse event measurement. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector.
Time frame: 6 weeks
Three 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. The toxicity will be evaluated as per the NCI Common Toxicity criteria version 2.0.Any toxicity scored as Grade 3 or 4 according to this criteria will be classified as an adverse event. If no toxicity is observed in the first three patients then we will enroll another three patients at the next dose level. However, if toxicity is observed in no more than one out of the three patients then three more patients will be enrolled at the same dose level. Now if the toxicity is observed in no more than one out of the six patients then we will advance to the next dose level and enroll three new patients. If toxicity is observed in two or more patients out of six then the dose limiting toxicity (DLT) has been exceeded and the previous dose level will be considered as the maximum tolerated dose (MTD) level.
To determine the feasibility of generating EBV specific cytotoxic T cell lines from patients with active EBV positive Lymphoma including Hodgkin Disease (HD) or Non-Hodgkin Lymphoma (NHL).
Time frame: 6 weeks
To determine the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines.
Time frame: 15 years
During the course of the study the survival, immunological efficacy and anti-tumor activity of neomycin resistance gene marked EBV specific cytotoxic T-lymphocyte lines will also be studied. In order to gain reasonable insight into the anti-tumor activity and late toxicity the patients will be followed for a total of twelve weeks.In the present case, the chances of observing any late toxicity should be if anything lower, as in this case the CTLs will be derived autologously.
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 15 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.
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 Injection of EBV Specific CTLs in people with Epstein-Barr Virus-Related Hodgkin Lymphoma and Epstein-Barr Virus-Related Non-Hodgkin Lymphoma, 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 10 inclusion and 9 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 15 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?
The safety of two IV injections of auto EBV specific CTLs will be determined through adverse event measurement. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector. (time frame: 6 weeks). The study lists 3 primary outcomes in all. 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 15 Feb 2017.