112 Clinical Trials for Various Conditions
Background: Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis, commonly known as mono. EBV infects more than 90% of the world s population. Mono can be serious, and it can lead to severe illnesses like cancer and autoimmune diseases. Researchers want to test vaccines that may help prevent EBV and associated diseases. Objective: To test two EBV vaccines: EBV gH/gL/gp42-ferritin and EBV gp350-ferritin. Eligibility: Healthy EBV-negative or EBV-positive people aged 18 to 29. Design: Participants will be screened. They will have a physical examination. They will give blood and saliva samples. They will receive 3 doses of the study vaccine as an injection in the shoulder muscle. They will get either one vaccine or a combination of both vaccines. Participants will get their first dose of the vaccine at visit 1, the second dose about 30 days later, and the final dose about 90 days after that. Participants will be given a memory aid so they can record any symptoms and side effects between visits. This can be done either on paper or online through a link that is emailed to them. There are 6 required in-person visits. There are also 2 optional visits. In between the in-person visits are 7 telehealth visits or phone calls. Each visit may take up to 4 hours. The study will last for about 17 months. Participants will have the option of staying in the study for an additional year.
To evaluate the anti cancer effect of VK 2019 in subjects with EBV related nasopharyngeal carcinoma (NPC) for whom there is no other standard treatment available
This study is for patients that have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease which has come back or has not gone away after treatment, including the best treatment the investigators know for these diseases. Some patients with Lymphoma or T/NK-lymphoproliferative disease show signs of virus that is sometimes called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono") 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 plays a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. T cells have been used to treat patients with cancers. T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor. The investigators have treated over 80 people on studies using T cells to target these diseases. About half of those patients who had disease at the time they got the cells had responses including some patients with complete responses. The investigators think that if T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected tumor cells. Therefore, in this study the investigators will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. The investigators know that T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion into the body. The investigators have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and additionally to evaluate how long they can be detected in the blood and what affect they have on cancer.
Background: Epstein-Barr virus (EBV) causes most cases of infectious mononucleosis (mono). Up to 1 in 10 people who get mono can have fatigue that lasts more than 6 months. One out of 100 people can have severe complications. EBV is also associated with several types of cancer. Researchers want to test an EBV vaccine. Objective: To test the safety of and immune response to a new vaccine against EBV. Eligibility: Healthy adults ages 18-29 Design: Participants will be screened with a medical history and physical exam. They will give a blood sample. Screening tests will be repeated during the study. Participants will get a dose of the study vaccine as an injection in a muscle in the upper arm. They will be observed for 30 to 60 minutes. Blood pressure, heart rate, breathing rate, and temperature will be checked. The injection site will be examined. Participants will get a diary card. They will write down any side effects they have after the vaccine dose, or they may use an electronic diary card. Participants will be asked to write down or enter any important medical events that may occur at any time during the study. Participants will get a vaccine dose at 2 more study visits. They will have 4 follow-up visits at different times after a vaccine dose. Participants will have 6 telephone calls in between the in-person visits. They will also have 1 telephone call 1 year after the third dose of vaccine. If possible, this visit can occur in person. Participation will last about 18 months. There is an optional in-person visit or telephone call 2 years after the third dose of vaccine.
VK-2019-001 is a 1/2a trial of the oral EBNA-1 targeting agent VK-2019 in patients with EBV-positive recurrent or metastatic NPC to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D), as well as to evaluate the PK profile of VK-2019.
To investigate the efficacy of autologous Epstein-barr virus (EBV)-specific T cells for the treatment of EBV positive Diffuse Large B Cell Lymphoma (DLBCL), Hodgkin Lymphoma (HL) and Post-transplant Lymphoproliferative Disease (PTLD) after failing first line treatment.
To investigate the efficacy of autologous EBV-specific T-cells for the treatment of patients with aggressive EBV positive extranodal NK/T-cell lymphoma
The subjects eligible for this trial have a type of blood cell cancer, other blood disease or a genetic disease for which they will receive a stem cell transplant. The donor of the stem cells will be either the subject's brother or sister, or another relative, or a closely matched unrelated donor. The Investigators are asking subjects to participate in this study which tests if blood cells from the subject's donor that have been grown in a special way, can prevent or be a effective treatment for early infection by five viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus, BK virus (BKV) and human herpes virus 6 (HHV6). The Investigators have grown T cells from the subject's stem cell donor in the laboratory in a way that will train them to recognize the viruses and control them when the T cells are given after a transplant. This treatment with specially trained T cells (also called cytotoxic T cells or "CTLs") has had activity against three of these viruses (CMV, EBV and Adenovirus) in previous studies. In this study the Investigators want to see if they increase the number of viruses that can be targeted to include BKV and HHV6 using a simple and fast approach to make the cells. The Investigators want to see if they can use a kind of white blood cell called T lymphocytes (or T cells) to prevent and treat adenovirus, CMV, EBV, BKV and HHV6 in the early stages of reactivation or infection.
Subjects have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease or severe chronic active Epstein Barr Virus (CAEBV) which has come back, is at risk of coming back, or has not gone away after treatment, including the best treatment we know for these diseases. Some of these patients show signs of virus that is called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono" or the "kissing disease") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells and some immune system 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 GRALE T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor. We have used this sort of therapy to treat a different type of cancer 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 lab that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However, in HD and NHL, T/NK-lymphoproliferative disease, and CAEBV, the tumor cells and B cells only express 4 EBV proteins. In a previous study, we made T cells that recognized all 9 proteins and gave them to patients with HD. Some patients had a partial response to this therapy but no patients had a complete response. We then did follow up studies where we made T cells that recognized the 2 EBV proteins seen in patients with lymphoma, T/NK-lymphoproliferative disease and CAEBV. We have treated over 50 people on those studies. About 60% of those patients who had disease at the time they got the cells had responses including some patients with complete responses. This study will expand on those results and we will try and make the T cells in the lab in a simpler faster way. These cells are called GRALE T cells. These GRALE T cells are an investigational product not approved by the FDA. The purpose of this study is to find the largest safe dose of LMP-specific cytotoxic GRALE T cells created using this new manufacturing technique. We will learn what the side effects are and to see whether this therapy might help patients with HD or NHL or EBV associated T/NK-lymphoproliferative disease or CAEBV.
Post transplant lymphoproliferative disease (PTLD) is a type of B-cell non-Hodgkin lymphoma that occurs in patients with weakened immune systems due to immunosuppressive medications taken after organ or stem cell transplantation. This is usually related to a virus called Epstein-Barr (EPV). Rituximab is a type of drug called an "antibody" that specifically destroys both normal and cancerous B-cells, and is commonly used for PTLD. Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) to treat multiple myeloma and a B-cell non-Hodgkin lymphoma called Mantle Cell Lymphoma, and shows significant activity in lymphoma cells caused by EBV. In this research study, we hope to learn if the addition of bortezomib to rituximab treatment can increase the rate of complete remissions and cures of PTLD after organ or stem cell transplant.
The purpose of this study determine whether the drug valganciclovir has a significant and real benefit on the central core of symptoms experienced by patients who have high titers to EBV and HHV-6 and are experiencing long-standing fatigue and cognitive impairment (CFS). In addition, to characterize a quantifiable biological marker in these patients that will facilitate the identification of those likely to respond to valganciclovir and will make it possible to assess response to treatment.
To determine the safety of the combination of CD45 monoclonal antibody (Mab) followed by intravenous injection of EBV specific CTL in patients with nasopharyngeal cancer. To compare the expansion, persistence and anti-tumor effects of the EBV specific CTL given after CD45 Mab administration with that observed in our first study. To obtain preliminary information on the safety and response to an extended dosage regimen of EBV-specific CTL in patients, who have stable disease or a partial response after the initial dose of EBV-specific CTL.
This protocol is broken up into 2 portions to determine the maximum tolerated dose for treating patients with a type of lymph gland disease. The 1st portion, called ALASCER are for people with a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma or Lymphoepithelioma which has returned or may return or has not gone away after treatment, including the best treatment we know for Lymphoma. While the 2nd portion (ALCI) also includes Lymphoepithelioma, severe chronic active EBV (SCAEBC), and leiomyosarcoma. Some patients with Lymphoma 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. Investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in your blood and affect the tumor. The investigators have 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. The investigators 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 disease and non-Hodgkin Lymphoma and SCAEBV, the tumor cells and B cells only express 2 EBV proteins. In a previous study we made T cells that recognized all 9 proteins and gave them to patients with Hodgkin disease. Some patients had a partial response to this therapy but no patients had a complete response. Investigators 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 we are trying to find out if we can improve this treatment by growing T cells that only recognize one of the proteins expressed on infected EBV Lymphoma cells called LMP-2a, and B cells called LMP1 and LMP2. These special T cells are called LMP specific cytotoxic T-lymphocytes (CTLs). The purpose of the study is to find the largest safe dose of LMP specific cytotoxic T cells, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease, non-Hodgkin Lymphoma, Lymphoepithelioma, SCAEBV or leiomyosarcoma.
This is a Phase Ib in adult patients with relapsed or refractory EBV-positive DLBCL using daily oral dosing of VK-2019 in three dose escalation cohorts: 600 mg/day, 1200 mg/day, 1800 mg/day for 28 days (cycle), until progression or toxicity.
This clinical trial tests the effect of induction chemotherapy response-guided radiation (de-escalated intensity-modulated radiation therapy \[IMRT\]) compared to standard IMRT in patients with Epstein-Barr virus (EBV)-associated nasopharyngeal cancer. Intensity-modulated radiation therapy (IMRT) is an advanced form of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Radiation therapy sometimes causes unwanted symptoms or side effects, including late effects such as hearing loss and dental problems. The severity of the side effects is related to the radiation dose received and the amount of tissue that received radiation. De-escalation IMRT uses lower doses of radiation based on a good response to induction chemotherapy. Giving de-escalated IMRT may be as effective as standard doses of IMRT in treating patients with EBV-associated nasopharyngeal cancer.
The purpose of the research is to test the safety and efficacy of the investigational drug in human subjects with cancer.
This study involves patients that have a cancer called diffuse large B cell lymphoma (DLBCL), Natural killer/T-cell lymphoma (NKTL), or classical Hodgkin lymphoma (cHL) (referred to collectively as lymphoma). Patients' lymphoma has come back or not gone away after treatment. A previous research study at Baylor combined two ways of fighting disease: antibodies and T cells. Antibodies are proteins that bind to bacteria, viruses and other foreign substances to prevent disease. T-cells are special infection-fighting white blood cells that can kill tumor cells or cells infected with bacteria and viruses. Both have shown promise treating cancer, but neither has been strong enough to cure most patients. In the previous study, an antibody called anti-CD30 which is found on the surface of some T-cells and cancer cells, and had been used to treat lymphoma with limited success, was joined to the T-cells through a process called gene transfer, resulting in CD30.CAR T cells. Another study saw encouraging responses using CD30.CAR T cells made in a lab from a patients' own blood then injected back into the same patient to treat their lymphoma. These cells are termed 'autologous' because they're given back to the original patient. In an ongoing study, patients were treated with allogeneic CD30.CAR T cells, which are made from healthy donors instead of the patients. The use of allogenic cells avoids a lengthy manufacture time since the products are stored as a bank and available on demand. This ongoing trial has preliminarily shown promising clinical activity with no safety concerns. With the current study, investigators plan to extend the anti-cancer effects of the CD30.CAR T cell by attaching another molecule called C7R, which has made CAR T cells have deeper and longer anticancer effects in the laboratory. The aim is to study the safety and effectiveness of allogeneic banked CD30.CAR-EBVST cells that also carry the C7R molecule, to learn the side effects of C7R modified CD30.CAR-EBVST cells in lymphoma patients, and to see whether this therapy may help them. As an extra safety step, the C7R containing T cells will also have a marker called iC9. If a patient experiences intolerable side effects from the C7R T cells, they could receive a medication called 'rimiducid' that can eliminate the C7R containing T cells by binding iC9, thereby potentially resolving the side effects. While not yet FDA approved, rimiducid has been tested in patients before without bad side effects.
The purpose of this study is to evaluate the safety and reactogenicity of mRNA-1195 in healthy participants.
Background: Epstein-Barr virus (EBV) causes most cases of infectious mononucleosis (mono). Mono can cause fatigue that lasts more than 6 months, and some people can have severe complications. EBV infection may also contribute to some cancers and autoimmune diseases. Currently, there are no approved therapies or vaccines for EBV infection. Objective: To test a vaccine against EBV. Eligibility: Healthy people aged 18 to 25 years. Design: Participants will be screened in 2 parts. They will have a blood test. If that test shows they have never had an EBV infection, they will have a second clinic visit. They will have a physical exam, with blood and urine tests. A cotton swab will be rubbed on their gums to collect saliva. Participants will receive 2 injections into a shoulder muscle. Some will receive the EBV vaccine. Others will receive a placebo; this contains harmless salt water with no vaccine. Participants will not know which one they are getting. The 2 injections will be 30 days apart. Participants will be asked to record any side effects or symptoms they have between visits. They can do this on paper or online. Participants will return for a follow-up visit 60 days after the first injection. They will have follow-up visits by phone or telehealth after 5 and 8 months. They will return for a physical exam after 13 months. They may come back for an optional physical exam after 2 years. Participants will come to the clinic if they become ill with an EBV infection during the study.
This study will evaluate the safety and efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive solid tumors and in combination with pembrolizumab in patients with recurrent/metastatic nasopharyngeal carcinoma
The main objective of Part A of this trial is to evaluate the safety and reactogenicity of mRNA-1189 in 18- to 30-year-old healthy adults, the main objective of Part B is to evaluate the safety and reactogenicity of mRNA-1189 in 12- to \<18-year-old healthy EBV-seronegative adolescents, and the main objective of Part C is to evaluate the safety and reactogenicity of mRNA-1189 in 10- to 21-year-old healthy adolescents and adults.
A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas
This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL) or classical Hodgkin lymphoma (cHL) (hereafter these 3 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study. In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins. The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients
The purpose of this study is to use VSTs (virus-specific T cells) from a donor that is a partial HLA (human leukocyte antigen) match with the patient to treat viral infections after an allogeneic hematopoietic stem cell transplant (HSCT). These cells may also have value in CAR-T recipients who have received a product that depletes virus specific T cells. The patient must have had a myeloablative or non-myeloablative allogeneic HSCT using either bone marrow, single/double umbilical cord blood, or peripheral blood stem cells (PBSC) or CAR T cell product targeting an antigen expressed on virus specific T cells. After a transplant, while the immune system grows back, the patient is at risk for infection. Some viruses can stay in the body for life and are normally controlled by a healthy immune system, but if the immune system is weakened, like after a transplant, they can cause life threatening infections. He/she must have had an infection with one or more of the following viruses -Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus (AdV), Human polyomavirus type I (BKV), and human polyomavirus type II (JCV)- that has persisted or recurred despite standard therapy. In this study, the investigators want to use white blood cells that have been trained to treat viral infections. In an earlier study the investigators showed that treatment with such specially trained T cells has been successful when the cells are made from the transplant donor. However as it takes 1-2 months to make the cells, that approach is not practical for patients who already have an infection. In a subsequent study, the investigators were able to create multivirus-specific T cells (VSTs) from the blood of healthy donors and created a bank of these cells. The investigators then successfully used these banked cells to treat virus infections after a stem cell transplant. In this study the investigators have further modified their production method to decrease the potential side effects and the investigators want to find out if they can use these banked VSTs to fight infections caused by the viruses mentioned above.
This is a multicenter, open-label, single-arm Phase 1B/2 study to assess the safety and efficacy of tabelecleucel in combination with pembrolizumab for the treatment of subjects with platinum-pretreated, recurrent/metastatic Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC).
This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating. The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al.
To determine the safety and efficacy (overall response rate) of pembrolizumab in patients with relapsed or refractory ENKTL, and EBV-DLBCL
A two part, Phase 1b/2 study to define a recommended Phase 2 dose of VRx-3996 in combination with valganciclovir (Phase 1b) designed to evaluate the efficacy of this combination in relapsed/refractory Epstein-Barr Virus Associated Lymphoma (EBV+ lymphomas).
The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Related donor Epstein-Barr Virus (EBV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults with refractory EBV infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant. Funding Source: FDA OOPD