Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00078533
Status:
COMPLETED
Last Update Posted:
2014-10-08
First Post:
2004-03-01
Brief Title:
Cytotoxic T-Lymphocytes for the Prophylaxis of Cytomegalovirus After Allogeneic Stem Cell Transplant
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Virus Specific Cytotoxic T-Lymphocytes for the Treatment of CMV After Allogeneic Stem Cell Transplant A Dose-Finding Trial
Status:
COMPLETED
Status Verified Date:
2014-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
VICTA
Brief Summary:
Patients 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 a brother or sister or another relative or a closely matched unrelated donor We are asking patients to participate in this study which tests if blood cells from the donor that have been grown in a special way can prevent the patients from getting an infection with a virus called Cytomegalovirus or CMV
CMV is a virus that can cause serious infections in patients with suppressed immune systems It usually affects the lungs and can cause a very serious pneumonia but it can also affect the intestinal tract the liver and the eyes Approximately 23 of normal people harbor this virus in their body In healthy people CMV rarely causes any problems because the immune system can keep it under control If the patient andor their donor is positive for CMV they are at risk of developing CMV disease while the patients immune system is weak post transplant Usually this risk is highest during the first 3-4 months after the transplant
CMV disease can be prevented during this time in most people by using drugs that can kill the virus such as Ganciclovir Foscarnet or Cidofovir However these medications have many side effects and have to be given daily by vein for approximately 4-5 months after transplant One of the side effects is that it takes the new immune system much longer to develop an effective defense against the virus Therefore once the medicines are stopped the patients still have a chance to develop CMV disease
We want to see if we can use a kind of white blood cell called T cells that we have grown from the stem cell donor instead of the regular treatment with Ganciclovir or Foscarnet to prevent CMV from flaring up These cells have been trained to attack CMV virus infected cells We will grow these T cells from blood taken from the donor before the patients transplant These cells are called CMV-specific cytotoxic T-lymphocytes or CMV CTL and they will be given to the patient around 30 days after their transplant
We have used this sort of therapy to treat a different virus which can cause problems after transplant called Epstein Barr Virus EBV Doctors at other places have used similar T cells to treat or prevent CMV infections after transplant and have not seen any significant problems These CMV specific cytotoxic T cells are an investigational product not approved by the Food and Drug Administration
CMV is a virus that can cause serious infections in patients with suppressed immune systems It usually affects the lungs and can cause a very serious pneumonia but it can also affect the intestinal tract the liver and the eyes Approximately 23 of normal people harbor this virus in their body In healthy people CMV rarely causes any problems because the immune system can keep it under control If the patient andor their donor is positive for CMV they are at risk of developing CMV disease while the patients immune system is weak post transplant Usually this risk is highest during the first 3-4 months after the transplant
CMV disease can be prevented during this time in most people by using drugs that can kill the virus such as Ganciclovir Foscarnet or Cidofovir However these medications have many side effects and have to be given daily by vein for approximately 4-5 months after transplant One of the side effects is that it takes the new immune system much longer to develop an effective defense against the virus Therefore once the medicines are stopped the patients still have a chance to develop CMV disease
We want to see if we can use a kind of white blood cell called T cells that we have grown from the stem cell donor instead of the regular treatment with Ganciclovir or Foscarnet to prevent CMV from flaring up These cells have been trained to attack CMV virus infected cells We will grow these T cells from blood taken from the donor before the patients transplant These cells are called CMV-specific cytotoxic T-lymphocytes or CMV CTL and they will be given to the patient around 30 days after their transplant
We have used this sort of therapy to treat a different virus which can cause problems after transplant called Epstein Barr Virus EBV Doctors at other places have used similar T cells to treat or prevent CMV infections after transplant and have not seen any significant problems These CMV specific cytotoxic T cells are an investigational product not approved by the Food and Drug Administration
Detailed Description:
If the patient and their donor are eligible we will take 100-120 ml 20-24 teaspoonfuls of blood from the donor 3-4 weeks before the transplant We will only take as much blood as is safe for the patient and their donor
We will use this blood to grow T cells We will first infect the peripheral blood mononuclear cells with a specially produced human virus adenovirus that carries part of the CMV gene to the monocytes which will stimulate the T cells This stimulation will train the T cells to kill cells with the pp65 from the CMV virus on their surface If this approach is insufficient to stimulate T cells which will kill the pp65 from the CMV virus then we will grow a special type of cell called dendritic cells which will stimulate the T cells and we will put the specially produced human virus adenovirus that carries the parts of the CMV gene called pp65 into the dendritic cells These dendritic cells will then be treated with radiation so they cannot grow They will then be used to stimulate T cells This stimulation will train the T cells to kill cells with the pp65 from the CMV virus on their surface
We will then grow these CMV specific CTLs by more stimulation with EBV infected cells which we will make from the blood of the donor by infecting them with EBV in the laboratory We will also put the adenovirus that carries the CMV pp65 gene into these EBV infected cells so that they too have CMVpp65 These EBV infected cells will be treated with radiation so they cannot grow Once we have made sufficient numbers of T cells we will test them to make sure they kill cells with CMVpp65 on their surface To make sure that these cells wont attack the patients tissues we test these cells against the lymphoblasts that we grow in the laboratory These will be used to check if the CMV CTL can attack them Alternatively we could take a small piece of skin from the patient to grow skin cells which can also be used to check if CMV CTL can attack them The skin biopsy can be done at the same time of another procedure such as a bone marrow
The donors CMV CTL cells will be thawed and injected into the patients intravenous line for a period of 10 minutes after the patient received Benadryl and Tylenol The patient will receive the dose of CMV CTL cells on or after day 30 following their transplant if they agree and are well enough We will not give antiviral medications during this study but we will monitor the CMV levels weekly for at least 30 days after the transplant If after the initial dose of CMV CTL cells the patient develops a viral infection then they may be eligible to receive one additional injection of CTLs at the same dose as the first injection If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir Foscarnet or Cidofuvir
The patient will continue to be followed in the BMT clinic after the injection They will be seen in the clinic in the hospital or contacted by the research nurse and have blood tests to monitor the blood counts the kidney and liver function and to monitor for viruses weekly for the first 60 days after the CTL infusion then at 3 6 9 and 12 months To learn more about the way the T cells are working in the body an extra 20-40 mls 4-8 teaspoons of blood will be taken before the infusion and then 24 hours after the infusion optional depending on the patients preference and then at 1 2 4 and 6 weeks after the infusion After this blood will be taken every 3 months for 1 year The amount of blood taken in the first 12 months will be 260-460mls 1-2 cups Total time participation for this study will be 1 year
We will use this blood to grow T cells We will first infect the peripheral blood mononuclear cells with a specially produced human virus adenovirus that carries part of the CMV gene to the monocytes which will stimulate the T cells This stimulation will train the T cells to kill cells with the pp65 from the CMV virus on their surface If this approach is insufficient to stimulate T cells which will kill the pp65 from the CMV virus then we will grow a special type of cell called dendritic cells which will stimulate the T cells and we will put the specially produced human virus adenovirus that carries the parts of the CMV gene called pp65 into the dendritic cells These dendritic cells will then be treated with radiation so they cannot grow They will then be used to stimulate T cells This stimulation will train the T cells to kill cells with the pp65 from the CMV virus on their surface
We will then grow these CMV specific CTLs by more stimulation with EBV infected cells which we will make from the blood of the donor by infecting them with EBV in the laboratory We will also put the adenovirus that carries the CMV pp65 gene into these EBV infected cells so that they too have CMVpp65 These EBV infected cells will be treated with radiation so they cannot grow Once we have made sufficient numbers of T cells we will test them to make sure they kill cells with CMVpp65 on their surface To make sure that these cells wont attack the patients tissues we test these cells against the lymphoblasts that we grow in the laboratory These will be used to check if the CMV CTL can attack them Alternatively we could take a small piece of skin from the patient to grow skin cells which can also be used to check if CMV CTL can attack them The skin biopsy can be done at the same time of another procedure such as a bone marrow
The donors CMV CTL cells will be thawed and injected into the patients intravenous line for a period of 10 minutes after the patient received Benadryl and Tylenol The patient will receive the dose of CMV CTL cells on or after day 30 following their transplant if they agree and are well enough We will not give antiviral medications during this study but we will monitor the CMV levels weekly for at least 30 days after the transplant If after the initial dose of CMV CTL cells the patient develops a viral infection then they may be eligible to receive one additional injection of CTLs at the same dose as the first injection If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir Foscarnet or Cidofuvir
The patient will continue to be followed in the BMT clinic after the injection They will be seen in the clinic in the hospital or contacted by the research nurse and have blood tests to monitor the blood counts the kidney and liver function and to monitor for viruses weekly for the first 60 days after the CTL infusion then at 3 6 9 and 12 months To learn more about the way the T cells are working in the body an extra 20-40 mls 4-8 teaspoons of blood will be taken before the infusion and then 24 hours after the infusion optional depending on the patients preference and then at 1 2 4 and 6 weeks after the infusion After this blood will be taken every 3 months for 1 year The amount of blood taken in the first 12 months will be 260-460mls 1-2 cups Total time participation for this study will be 1 year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| VICTA | OTHER | None | None |
| PACT 001 | OTHER_GRANT | NHLBI | None |