Hodgkin DiseasePhase 1ALCI2NCT01956084
Cytotoxic T Cells to Treat Relapsed EBV-positive Lymphoma
A Phase 1 study testing LMP1/2 CTLs (Group A) and LMP1/2 CTLs (Group B) in people with Hodgkin Disease and Non Hodgkin Lymphoma, run by Catherine Bollard at 1 site in United States.
Trial summary
In this study, investigators are trying to see if LMP specific cytotoxic T lymphocytes (CTLs) will prevent or treat disease called Epstein Barr Virus (EBV) Disorder including either Hodgkin Lymphoma or non-Hodgkin Lymphoma or Lymphoepithelioma or severe chronic active EBV infection syndrome (SCAEBV) or Leiomyosarcoma… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hodgkin Disease, Non Hodgkin Lymphoma, Lymphoepithelioma
- What is being tested?
- LMP1/2 CTLs (Group A) and LMP1/2 CTLs (Group B)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2013to 15 Oct 2019
- 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, regardless of age or sex, with a diagnosis of EBV positive Hodgkin's or non-Hodgkin's Lymphoma or EBV (associated)-T/NK-LPD lymphoproliferative disease or Lymphoepithelioma/leiomyosarcoma regardless of histological subtype or Severe Chronic EBV and in remission (group A) or with detectable disease (group B) after allogeneic SCT
- Patients with life expectancy > 6 weeks.
- Tumor tissue EBV positive
- Patients with a Karnofsky/Lansky score of > 50
- Donor HIV negative
- must not have less than 50% donor chimerism in either peripheral blood or bone marrow
Show all 10Show fewer
- Patients with bilirubin <2x normal, AST <5x 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.
- Patient, parent/guardian able to give informed consent.
Who cannot join
- Donors who are HIV positive
- Patients with GVHD > Grade II
- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research.
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: ADMINISTRATION of LMP-SPECIFIC CYTOTOXIC T-LYMPHOCYTES to PATIENTS with RELAPSED EBV-POSITIVE LYMPHOMA
In this study, investigators are trying to see if LMP specific cytotoxic T lymphocytes (CTLs) will prevent or treat disease called Epstein Barr Virus (EBV) Disorder including either Hodgkin Lymphoma or non-Hodgkin Lymphoma or Lymphoepithelioma or severe chronic active EBV infection syndrome (SCAEBV) or Leiomyosarcoma which has come back or has not gone away after treatment, including the best treatment. Investigators are using special immune system cells called third party LMP specific cytotoxic T lymphocytes (CTLs), a new experimental therapy.
Some patients with Lymphoma or SCAEBV or Leiomyosarcoma 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 up to half the patients with Hodgkin's and non-Hodgkin Lymphoma, suggesting that it may play a role in causing Lymphoma. The cancer cells (in lymphoma) and some B cells (in SCAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. The investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in patient's blood and affect the tumor or infection.
Read more
Investigators used this sort of therapy to treat a different type of cancer that occurs after bone marrow or solid organ transplant called post transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. They grew T cells in the laboratory that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However in Hodgkin Lymphoma, the tumor cells and B cells only express 2 EBV proteins. In a previous study they made T cells that recognized all 9 proteins and gave them to patients with Hodgkin Lymphoma. Some patients had a partial response to this therapy but no patients had a complete response. They think one reason may be that many of the T cells reacted with proteins that were not on the tumor cells. In this present study the investigators are trying to find out if the investigators can improve this treatment by growing T cells that recognize proteins expressed on EBV infected Lymphoma cells and B cells called LMP-1 and LMP2. These special T cells are called third party LMP 1/2 -specific cytotoxic T-lymphocytes (CTLs). These LMP-specific cytotoxic
T cells are an investigational product not approved by the Food and Drug Administration.
Read the detailed description
Investigators will first test a biopsy of the tumor or lymph node that has already been done to see if the tumor or tissue cells are EBV positive. If the patient is eligible, investigators will then take 60 mL (about 12 teaspoons) of blood from the patient or their donor on one or two occasions. They will use this blood to grow T cells. First they will grow a special type of cells called dendritic cells or monocytes which will stimulate the T cells. Next they will put a specially produced human virus that carries the LMP genes into the dendritic cells or monocytes. They will then be used to stimulate T cells. This stimulation will train the T cells to kill cells with LMP on their surface. Investigators will then grow these LMP specific CTLs by more stimulation with EBV infected cells. These EBV infected cells will be treated with radiation so they cannot grow.
Once sufficient numbers of T cells have been made, investigators will test them to make sure they kill cells with LMP on their surface. If the counts are low they may need to obtain additional blood samples to make these cells. Prior to giving the patient the CTLs, the cells will be tested to make sure they don't attack the tissue.
The cells will then be thawed and injected into the patient over 10 minutes. 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 lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up to six additional doses of the T cells if the patient wishes. This is a dose escalation study which means that for some patients the second dose may be larger than the first. All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or the Methodist Hospital.
For follow-up after the CTL infusions, the patient will be seen every 3 months for the first year. Then the patient will either be seen in the clinic or they will be contacted by a research nurse yearly for 5 years.
- Conditions
- Hodgkin Disease, Non Hodgkin Lymphoma, Lymphoepithelioma, Severe Chronic Active EBV Infection Syndrome (SCAEBV), Leiomyosarcoma
- Being tested
- LMP1/2 CTLs (Group A), LMP1/2 CTLs (Group B)
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Leiomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LMP1/2 CTLs (Group A)Drug
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules:
Dose Level One:
Day 0: 1 x 107 cells/m2 Day 14: 1 x 107 cells/m2
Dose Level Two:
Day 0: 2 x 107 cells/m2 Day 14: 2 x 107 cells/m2
Dose Level Three:
Day 0: 5 x 107 cells/m2 Day 14: 5 x 107 cells/m2
LMP1/2 CTLs (Group B)Drug
Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules:
Dose Level One:
Day 0: 1 x 107 cells/m2 Day 14: 1 x 107 cells/m2
Dose Level Two:
Day 0: 2 x 107 cells/m2 Day 14: 2 x 107 cells/m2
Dose Level Three:
Day 0: 5 x 107 cells/m2 Day 14: 5 x 107 cells/m2
| Study group | Role | What they receive |
|---|---|---|
| LMP1/2 CTLs (Group A) | Experimental | Patients receiving CTLs as adjunctive therapy following allogeneic stem transplant Receives: Drug: LMP1/2 CTLs (Group A) |
| LMP1/2 CTLs (Group B) | Experimental | Patients receiving CTLs in relapse following allogeneic stem cell transplant Receives: Drug: LMP1/2 CTLs (Group B) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with dose limiting toxicity (DLT)
Toxicity will be evaluated according to NCI Common Terminology Criteria for Adverse Events scale, version 2.0. DLT will be defined as development of any toxicity scored as Grade 3 or 4 and primarily related to the CTL infusion.
Measured: 6 weeks
Secondary outcomes (1)
Survival and Immune Function of LMP-specific CTLs
Survival and function will be measured by frequencies and immunological parameters from (enzyme-linked immunospot) ELISPOT and cytotoxicity assays.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2013 (estimated)
- Study startNov 2013
- Primary completion19 Nov 2017
- Study completion15 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hodgkin DiseaseStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Bollard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Catherine Bollard, Children's National Research Institute
- Investigators
- Catherine Bollard, MD, Principal investigator, CNMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01956084
- Sponsor's protocol ID
- ALCI2
- Acronym
- ALCI2
- Status last verified
- Dec 2024
- First submitted
- 25 Sep 2013
- Last updated
- 19 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McLaughlin LP, Rouce R, Gottschalk S, Torrano V, Carrum G, Wu MF, Hoq F, Grilley B, Marcogliese AM, Hanley PJ, Gee AP, Brenner MK, Rooney CM, Heslop HE, Bollard CM. EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation. Blood. 2018 Nov 29;132(22):2351-2361. doi: 10.1182/blood-2018-07-863654. Epub 2018 Sep 27.
PubMed 30262660
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ADMINISTRATION of LMP-SPECIFIC CYTOTOXIC T-LYMPHOCYTES to PATIENTS with RELAPSED EBV-POSITIVE LYMPHOMA
- ClinicalTrials.gov ID
- NCT01956084
- Acronym / sponsor ID
- ALCI2 / ALCI2
- Conditions
- Hodgkin Disease, Non Hodgkin Lymphoma, Lymphoepithelioma, Severe Chronic Active EBV Infection Syndrome (SCAEBV), Leiomyosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Catherine BollardUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- 19 Nov 2017 (actual)
- Study completion
- 15 Oct 2019 (actual)
- First posted
- 8 Oct 2013 (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.
In this study, investigators are trying to see if LMP specific cytotoxic T lymphocytes (CTLs) will prevent or treat disease called Epstein Barr Virus (EBV) Disorder including either Hodgkin Lymphoma or non-Hodgkin Lymphoma or Lymphoepithelioma or severe chronic active EBV infection syndrome (SCAEBV) or Leiomyosarcoma which has come back or has not gone away after treatment, including the best treatment. Investigators are using special immune system cells called third party LMP specific cytotoxic T lymphocytes (CTLs), a new experimental therapy.
Some patients with Lymphoma or SCAEBV or Leiomyosarcoma 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 up to half the patients with Hodgkin's and non-Hodgkin Lymphoma, suggesting that it may play a role in causing Lymphoma. The cancer cells (in lymphoma) and some B cells (in SCAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. The investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in patient's blood and affect the tumor or infection.
Investigators used this sort of therapy to treat a different type of cancer that occurs after bone marrow or solid organ transplant called post transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. They grew T cells in the laboratory that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However in Hodgkin Lymphoma, the tumor cells and B cells only express 2 EBV proteins. In a previous study they made T cells that recognized all 9 proteins and gave them to patients with Hodgkin Lymphoma. Some patients had a partial response to this therapy but no patients had a complete response. They think one reason may be that many of the T cells reacted with proteins that were not on the tumor cells. In this present study the investigators are trying to find out if the investigators can improve this treatment by growing T cells that recognize proteins expressed on EBV infected Lymphoma cells and B cells called LMP-1 and LMP2. These special T cells are called third party LMP 1/2 -specific cytotoxic T-lymphocytes (CTLs). These LMP-specific cytotoxic
T cells are an investigational product not approved by the Food and Drug Administration.
Detailed description
Investigators will first test a biopsy of the tumor or lymph node that has already been done to see if the tumor or tissue cells are EBV positive. If the patient is eligible, investigators will then take 60 mL (about 12 teaspoons) of blood from the patient or their donor on one or two occasions. They will use this blood to grow T cells. First they will grow a special type of cells called dendritic cells or monocytes which will stimulate the T cells. Next they will put a specially produced human virus that carries the LMP genes into the dendritic cells or monocytes. They will then be used to stimulate T cells. This stimulation will train the T cells to kill cells with LMP on their surface. Investigators will then grow these LMP specific CTLs by more stimulation with EBV infected cells. These EBV infected cells will be treated with radiation so they cannot grow.
Once sufficient numbers of T cells have been made, investigators will test them to make sure they kill cells with LMP on their surface. If the counts are low they may need to obtain additional blood samples to make these cells. Prior to giving the patient the CTLs, the cells will be tested to make sure they don't attack the tissue.
The cells will then be thawed and injected into the patient over 10 minutes. 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 lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up to six additional doses of the T cells if the patient wishes. This is a dose escalation study which means that for some patients the second dose may be larger than the first. All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or the Methodist Hospital.
For follow-up after the CTL infusions, the patient will be seen every 3 months for the first year. Then the patient will either be seen in the clinic or they will be contacted by a research nurse yearly for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LMP1/2 CTLs (Group A) | Experimental | Drug: LMP1/2 CTLs (Group A)Patients receiving CTLs as adjunctive therapy following allogeneic stem transplant |
| LMP1/2 CTLs (Group B) | Experimental | Drug: LMP1/2 CTLs (Group B)Patients receiving CTLs in relapse following allogeneic stem cell transplant |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Any patient, regardless of age or sex, with a diagnosis of EBV positive Hodgkin's or non-Hodgkin's Lymphoma or EBV (associated)-T/NK-LPD lymphoproliferative disease or Lymphoepithelioma/leiomyosarcoma regardless of histological subtype or Severe Chronic EBV and in remission (group A) or with detectable disease (group B) after allogeneic SCT
- Patients with life expectancy > 6 weeks.
- Tumor tissue EBV positive
- Patients with a Karnofsky/Lansky score of > 50
- Donor HIV negative
Key exclusion criteria (3 listed)
- Donors who are HIV positive
- Patients with GVHD > Grade II
- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research.
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 |
|---|---|---|
| LMP1/2 CTLs (Group A)Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One: Day 0: 1 x 107 cells/m2 Day 14: 1 x 107 cells/m2 Dose Level Two: Day 0: 2 x 107 cells/m2 Day 14: 2 x 107 cells/m2 Dose Level Three: Day 0: 5 x 107 cells/m2 Day 14: 5 x 107 cells/m2 | Drug | LMP1/2 CTLs (Group A) |
| LMP1/2 CTLs (Group B)Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One: Day 0: 1 x 107 cells/m2 Day 14: 1 x 107 cells/m2 Dose Level Two: Day 0: 2 x 107 cells/m2 Day 14: 2 x 107 cells/m2 Dose Level Three: Day 0: 5 x 107 cells/m2 Day 14: 5 x 107 cells/m2 | Drug | LMP1/2 CTLs (Group B) |
Primary outcome
Number of patients with dose limiting toxicity (DLT)
Time frame: 6 weeks
Toxicity will be evaluated according to NCI Common Terminology Criteria for Adverse Events scale, version 2.0. DLT will be defined as development of any toxicity scored as Grade 3 or 4 and primarily related to the CTL infusion.
1 secondary outcome
Survival and Immune Function of LMP-specific CTLs
Time frame: 5 years
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 19 Dec 2024.
- Derived from this study: PubMed 30262660McLaughlin LP, Rouce R, Gottschalk S, Torrano V, Carrum G, Wu MF, Hoq F, Grilley B, Marcogliese AM, Hanley PJ, Gee AP, Brenner MK, Rooney CM, Heslop HE, Bollard CM. EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation. Blood. 2018 Nov 29;132(22):2351-2361. doi: 10.1182/blood-2018-07-863654. Epub 2018 Sep 27.
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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.
Catherine Bollard, MD principal investigator
CNMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LMP1/2 CTLs (Group A) and LMP1/2 CTLs (Group B) in people with Hodgkin Disease and Non Hodgkin Lymphoma, run by Catherine Bollard at 1 site 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 3 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 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Number of patients with dose limiting toxicity (DLT) (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 NCT01956084, which also lists 1 linked publication.
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 19 Dec 2024.