Hodgkin LymphomaPhase 1MALTEDNCT01447056
Most Closely HLA-Matched CTLs for Relapsed Epstein Barr Virus(EBV)-Associated Diseases
A Phase 1 study testing LMP specific T cells in people with Hodgkin Lymphoma and Non-Hodgkin Lymphoma, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Patients have a type of a lymph node cancer called lymphoma, a tumor of the nasal passages called nasopharyngeal carcinoma (NPC), a tumor of a particular type of muscle called leiomyosarcoma (LMS) or a condition called severe chronic active EBV (SCAEBV) syndrome. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Lymphoproliferative Disorder
- What is being tested?
- LMP specific T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2012to 22 Jan 2020
- 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
- SCREENING:
- Any patient, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma - Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma - Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
- Karnofsky/Lansky score 50% or more.
- Informed consent explained to and signed by patient or parent/guardian able to give informed consent and given a copy.
- TREATMENT:
- Any patient, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma - Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma - Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
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- The disease needs to be in one of the following stages: - At diagnosis or in first relapse AND the patient is unable to receive conventional chemotherapy for his/her condition. - In second or subsequent relapse. - With residual disease after autologous, syngeneic or allogeneic HSCT.
- Life expectancy 6 weeks or more.
- Tumor tissue is positive for EBV.
- Karnofsky/Lansky score 50% or more.
- Bilirubin less than 3 times higher than the normal limits, AST less than 5 times higher than the normal limits, Hgb greater than 8.0 g/dL and serum creatinine less than 3 times higher than the normal limits.
- Pulse oximetry of greater than 90% on room air.
- If post allogeneic HSCT, patient must not have less than 50% donor chimerism in either peripheral blood or bone marrow.
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone at time of treatment.
- Informed consent explained to and signed by patient or parent/guardian able to give informed consent and given a copy.
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom.
Who cannot join
- SCREENING:
- 1. Known HIV positivity.
- TREATMENT:
- Currently receiving any investigational agents or have received any tumor vaccines within previous 4 weeks.
- Active acute grade III-IV graft-versus-host disease.
- Severe intercurrent infection.
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- Received alemtuzumab or other anti-T-cell antibody within 28 days.
- HIV seropositivity.
- Pregnancy (due to unknown effects of this therapy on a fetus) or lactation.
- Tumor in a location where enlargement could cause airway obstruction.
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: Most Closely HLA-Matched Allogeneic LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Relapsed EBV-Associated Diseases
Patients have a type of a lymph node cancer called lymphoma, a tumor of the nasal passages called nasopharyngeal carcinoma (NPC), a tumor of a particular type of muscle called leiomyosarcoma (LMS) or a condition called severe chronic active EBV (SCAEBV) syndrome. The disease has come back, may come back or has not gone away after treatment. This voluntary research study uses special immune system cells called LMP-specific cytotoxic T lymphocytes, a new experimental therapy.
Some patients with these diseases show evidence of infection with the virus that causes infectious mononucleosis (called Epstein-Barr virus, or EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of up to half of the patients with lymphomas, and in some cases of NPC and LMS, suggesting that it may play a role in causing these diseases. Those cancer cells (as well as some B cells in SCAEBV) that are 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 cells infected by EBV can survive in the blood and affect the tumor.
Read more
This treatment with specially trained T cells has had activity against these viruses when the cells are made from patients with those diseases (or, after bone marrow transplant, from the patient's transplant donor). However, sometimes it is not possible to grow these cells; other times, it may take 2 to 3 months to make the cells, which may be too long when one has an active tumor. We are therefore asking if subjects would like to participate in this study, which tests if blood cells from a donor that is a partial match with the subject (or the transplant donor) that have been grown in the way described above can survive in the blood and affect the disease.
These LMP-specific CTLs are an investigational product not approved by the Food and Drug Administration.
Read the detailed description
First, we will search our cell bank to see if there is a CTL line that is a match with the subject and his/her donor. This matching is done using HLA type, which measures 6 proteins on the cell surface. If HLA type has not been previously checked, we will do a blood draw (half to one tablespoon) so that this can be done.
These CTL lines have been made at Baylor College of Medicine from donors for other transplant patients or other normal donors from the National Marrow Donor Program. All donors have been screened in the same way that we screen blood donors. When the CTL lines were made, blood was taken from the donors and used to grow T cells. To do this, we first grew a special type of cells called dendritic cells or monocytes and we put a specially produced human virus (adenovirus) that carries the LMP genes into the dendritic cells or monocytes. They were then used to stimulate T cells. This stimulation trained the T cells to kill cells with LMP on their surface.
We then grew these LMP specific CTLs by more stimulation with EBV infected cells (made from the same blood). We also put the adenovirus that carries the LMP genes into these EBV infected cells so that we increased the amount of LMP that these cells had. These EBV infected cells were treated with radiation so they could not grow. Once we made sufficient numbers of T cells, we tested them to make sure they kill cells with LMP on their surface and froze them.
To make sure that these cells won't attack the subject's tissues, we will also test the cells against his/her own cells, which we will grow in the laboratory.
If the level of circulating T-cells in the patient is relatively high, s/he will receive one treatment of cyclophosphamide. This drug will decrease the numbers of the patient's own T-cells before the investigators infuse the LMP-specific cytotoxic T-lymphocytes. If the patient is already receiving chemotherapy, this may not be needed.
The LMP specific CTLs will be thawed and injected IV over 1-10 minutes. Initially, one dose of T-cells will be given. If after the first dose, there is a reduction in the size of the patient's disease, they can receive up to five additional doses of the T-cells if they wish.
This is a dose escalation study, which means that the doses of cells will be increased as more patients are treated, as long as the lower doses are determined to be safe.
- Conditions
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Lymphoproliferative Disorder, Nasopharyngeal Carcinoma, Leiomyosarcoma, Severe Chronic Active EBV (SCAEBV)
- Being tested
- LMP specific T cells
- Keywords
- Hodgkin lymphoma, Non-Hodgkin lymphoma, Lymphoproliferative disorder, Nasopharyngeal carcinoma, Leiomyosarcoma, EBV Cytotoxic T Lymphocytes
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoproliferative Disorders, Nasopharyngeal Carcinoma, Leiomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LMP specific T cellsBiological
Three dose levels will be evaluated:
Dose Level 1: 2×10^7 cells/m2; Dose Level 2: 1×10^8 cells/m2; Dose Level 3: 2×10^8 cells/m2
If patients have a partial response or have stable disease they will be eligible to receive up to 5 further doses of CTLs, each of which will consist of the same number as their first injection.
| Study group | Role | What they receive |
|---|---|---|
| LMP Specific T cells | Experimental | LMP specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line and the IV flushed with saline. The volume of infusion will depend upon the concentration of the cells when frozen, the dose level, and the size of the patient. Receives: Biological: LMP specific T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients with dose limiting toxicities after T-cell infusions
To determine the safety of intravenous injections of third-party, partially HLA- matched, allogeneic Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in patients with severe chronic active EBV (SCAEBV) infection or EBV-associated Hodgkin or non-Hodgkin lymphomas (HL/NHL), other lymphoproliferative disorders (LPD) or other malignancies (leiomyosarcoma and nasopharyngeal carcinoma)
Measured: 6 weeks
Secondary outcomes (3)
Safety and response to a repeated dosage regimen
To obtain preliminary information on the safety and response to a repeated dosage regimen.
Measured: 5 years
Analysis of immune function of CTLs
To determine the survival and the immune function of third-party allogeneic EBV-specific CTL lines
Measured: 5 years
Number of patients with an EBV and/or disease response to the CTLs
To assess anti-EBV and anti-tumor effects of third-party partially HLA- matched allogeneic EBV-specific CTL lines.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study startFeb 2012
- Primary completionMar 2015
- Study completion22 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 37 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, Carlos Ramos, Baylor College of Medicine
- Investigators
- Carlos A Ramos, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01447056
- Sponsor's protocol ID
- H-28361-MALTED
- Other IDs
- MALTED
- Acronym
- MALTED
- Status last verified
- Feb 2020
- First submitted
- 12 Aug 2011
- Last updated
- 7 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Most Closely HLA-Matched Allogeneic LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Relapsed EBV-Associated Diseases
- ClinicalTrials.gov ID
- NCT01447056
- Acronym / sponsor ID
- MALTED / H-28361-MALTED
- Conditions
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Lymphoproliferative Disorder, Nasopharyngeal Carcinoma, Leiomyosarcoma, Severe Chronic Active EBV (SCAEBV)
- Keywords
- Hodgkin lymphoma, Non-Hodgkin lymphoma, Lymphoproliferative disorder, Nasopharyngeal carcinoma, Leiomyosarcoma, EBV Cytotoxic T Lymphocytes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 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
- Feb 2012 (actual)
- Primary completion
- Mar 2015 (actual)
- Study completion
- 22 Jan 2020 (actual)
- First posted
- 5 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients have a type of a lymph node cancer called lymphoma, a tumor of the nasal passages called nasopharyngeal carcinoma (NPC), a tumor of a particular type of muscle called leiomyosarcoma (LMS) or a condition called severe chronic active EBV (SCAEBV) syndrome. The disease has come back, may come back or has not gone away after treatment. This voluntary research study uses special immune system cells called LMP-specific cytotoxic T lymphocytes, a new experimental therapy.
Some patients with these diseases show evidence of infection with the virus that causes infectious mononucleosis (called Epstein-Barr virus, or EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of up to half of the patients with lymphomas, and in some cases of NPC and LMS, suggesting that it may play a role in causing these diseases. Those cancer cells (as well as some B cells in SCAEBV) that are 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 cells infected by EBV can survive in the blood and affect the tumor.
This treatment with specially trained T cells has had activity against these viruses when the cells are made from patients with those diseases (or, after bone marrow transplant, from the patient's transplant donor). However, sometimes it is not possible to grow these cells; other times, it may take 2 to 3 months to make the cells, which may be too long when one has an active tumor. We are therefore asking if subjects would like to participate in this study, which tests if blood cells from a donor that is a partial match with the subject (or the transplant donor) that have been grown in the way described above can survive in the blood and affect the disease.
These LMP-specific CTLs are an investigational product not approved by the Food and Drug Administration.
Detailed description
First, we will search our cell bank to see if there is a CTL line that is a match with the subject and his/her donor. This matching is done using HLA type, which measures 6 proteins on the cell surface. If HLA type has not been previously checked, we will do a blood draw (half to one tablespoon) so that this can be done.
These CTL lines have been made at Baylor College of Medicine from donors for other transplant patients or other normal donors from the National Marrow Donor Program. All donors have been screened in the same way that we screen blood donors. When the CTL lines were made, blood was taken from the donors and used to grow T cells. To do this, we first grew a special type of cells called dendritic cells or monocytes and we put a specially produced human virus (adenovirus) that carries the LMP genes into the dendritic cells or monocytes. They were then used to stimulate T cells. This stimulation trained the T cells to kill cells with LMP on their surface.
We then grew these LMP specific CTLs by more stimulation with EBV infected cells (made from the same blood). We also put the adenovirus that carries the LMP genes into these EBV infected cells so that we increased the amount of LMP that these cells had. These EBV infected cells were treated with radiation so they could not grow. Once we made sufficient numbers of T cells, we tested them to make sure they kill cells with LMP on their surface and froze them.
To make sure that these cells won't attack the subject's tissues, we will also test the cells against his/her own cells, which we will grow in the laboratory.
If the level of circulating T-cells in the patient is relatively high, s/he will receive one treatment of cyclophosphamide. This drug will decrease the numbers of the patient's own T-cells before the investigators infuse the LMP-specific cytotoxic T-lymphocytes. If the patient is already receiving chemotherapy, this may not be needed.
The LMP specific CTLs will be thawed and injected IV over 1-10 minutes. Initially, one dose of T-cells will be given. If after the first dose, there is a reduction in the size of the patient's disease, they can receive up to five additional doses of the T-cells if they wish.
This is a dose escalation study, which means that the doses of cells will be increased as more patients are treated, as long as the lower doses are determined to be safe.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LMP Specific T cells | Experimental | Biological: LMP specific T cellsLMP specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line and the IV flushed with saline. The volume of infusion will depend upon the concentration of the cells when frozen, the dose level, and the size of the patient. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Any patient, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma - Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma - Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
- Karnofsky/Lansky score 50% or more.
- Informed consent explained to and signed by patient or parent/guardian able to give informed consent and given a copy.
- Any patient, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma - Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma - Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
- The disease needs to be in one of the following stages: - At diagnosis or in first relapse AND the patient is unable to receive conventional chemotherapy for his/her condition. - In second or subsequent relapse. - With residual disease after autologous, syngeneic or allogeneic HSCT.
Key exclusion criteria (10 listed)
- 1. Known HIV positivity.
- Currently receiving any investigational agents or have received any tumor vaccines within previous 4 weeks.
- Active acute grade III-IV graft-versus-host disease.
- Severe intercurrent infection.
- Received alemtuzumab or other anti-T-cell antibody within 28 days.
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 |
|---|---|---|
| LMP specific T cellsThree dose levels will be evaluated: Dose Level 1: 2×10^7 cells/m2; Dose Level 2: 1×10^8 cells/m2; Dose Level 3: 2×10^8 cells/m2 If patients have a partial response or have stable disease they will be eligible to receive up to 5 further doses of CTLs, each of which will consist of the same number as their first injection. | Biological | LMP Specific T cells |
Primary outcome
Patients with dose limiting toxicities after T-cell infusions
Time frame: 6 weeks
To determine the safety of intravenous injections of third-party, partially HLA- matched, allogeneic Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in patients with severe chronic active EBV (SCAEBV) infection or EBV-associated Hodgkin or non-Hodgkin lymphomas (HL/NHL), other lymphoproliferative disorders (LPD) or other malignancies (leiomyosarcoma and nasopharyngeal carcinoma)
3 secondary outcomes
Safety and response to a repeated dosage regimen
Time frame: 5 years
Analysis of immune function of CTLs
Time frame: 5 years
Number of patients with an EBV and/or disease response to the CTLs
Time frame: 6 weeks
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 2020.
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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.
Carlos A Ramos, 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 LMP specific T cells in people with Hodgkin Lymphoma and 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 16 inclusion and 10 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 2020. 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?
Patients with dose limiting toxicities after T-cell infusions (time frame: 6 weeks). 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 2020; AzTrials last refreshed its copy on 1 Nov 2026.