Cytomegalovirus InfectionsPhase 1VICTANCT00078533
Cytotoxic T-Lymphocytes for the Prophylaxis of Cytomegalovirus After Allogeneic Stem Cell Transplant
A Phase 1 study testing CMV CTL infusion in people with Cytomegalovirus Infections, run by Baylor College of Medicine at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- CMV CTL infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2004to Jun 2011
- 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
- Recipients of allogeneic donor stem cell transplants at risk for CMV reactivation with a CMV seropositive stem cell donor and at least 30 days post transplant.
- Recipients can have early evidence of CMV reactivation with greater than 2 leukocytes but less than 10 leukocytes positive for the CMV Ag per 100,000 cells.
- No evidence of graft-versus-host disease (GVHD) > Grade II at time of enrollment.
- Life expectancy > 30 days
- No severe intercurrent infections
- Lansky/Karnofsky scores greater than or equal to 60
Show all 10Show fewer
- Absence of severe renal disease (Creatinine > x 3 normal for age)
- Absence of severe hepatic disease (direct bilirubin > 3 mg/dl or SGOT > 500)
- Not receiving Ganciclovir, Foscarnet, or Cidofovir or other antiviral therapy for CMV reactivation
- Patient/guardian able to give informed consent
Who cannot join
- Patients with CMV negative stem cell donors
- Patients with GVHD Grades III-IV
- Patients receiving antiviral therapy for CMV reactivation or other viral infections such as adenovirus or herpes viruses
- Patients with significant CMV reactivation. Significant CMV reactivation is defined as one CMV Antigenemia reading with >10 leukocytes positive for the CMV Ag per 100,000 cells
- Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease
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: Virus Specific Cytotoxic T-Lymphocytes for the Treatment of CMV After Allogeneic Stem Cell Transplant: A Dose-Finding Trial
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 2/3 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 and/or 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.
Read more
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.
Read the 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 won't 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 donor's 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.
- Conditions
- Cytomegalovirus Infections
- Being tested
- CMV CTL infusion
- Keywords
- Allogeneic, Transplant, CMV, Stem Cell, Donor, Allogeneic stem cell recipients at risk for CMV reactivation
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV CTL infusionBiological
Three dose levels will be explored. The lowest dose level will be 1x10^7cells/m2 and the highest will be 1x10^8/m2. 3-6 pts will be entered at each dose level (depending on toxicity). If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval. Additional patients will be treated at dose level 1 in order to assess the secondary objective of virus-specific immunity from the CTL infusions
| Study group | Role | What they receive |
|---|---|---|
| CMV CTL infusion | Experimental | Subjects are assigned a dose level at the time of enrollment. Receives: Biological: CMV CTL infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety, toxicity and maximum tolerated dose (MTD)
Measured: 30 days
Efficacy of recovery of virus-specific immunity and correlation with protection from viral reactivation/disease.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2004 (estimated)
- Study startApr 2004
- Primary completionJul 2010
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies 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
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital Research Institute, National Heart, Lung, and Blood Institute (NHLBI)
- 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
- NCT00078533
- Sponsor's protocol ID
- 12683-VICTA
- Other IDs
- VICTA, PACT 001
- Acronym
- VICTA
- Status last verified
- Jun 2014
- First submitted
- 1 Mar 2004
- Last updated
- 8 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Keller MD, Darko S, Lang H, Ransier A, Lazarski CA, Wang Y, Hanley PJ, Davila BJ, Heimall JR, Ambinder RF, Barrett AJ, Rooney CM, Heslop HE, Douek DC, Bollard CM. T-cell receptor sequencing demonstrates persistence of virus-specific T cells after antiviral immunotherapy. Br J Haematol. 2019 Oct;187(2):206-218. doi: 10.1111/bjh.16053. Epub 2019 Jun 20.
PubMed 31219185Hanley PJ, Cruz CR, Savoldo B, Leen AM, Stanojevic M, Khalil M, Decker W, Molldrem JJ, Liu H, Gee AP, Rooney CM, Heslop HE, Dotti G, Brenner MK, Shpall EJ, Bollard CM. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood. 2009 Aug 27;114(9):1958-67. doi: 10.1182/blood-2009-03-213256. Epub 2009 May 14.
PubMed 19443656
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Virus Specific Cytotoxic T-Lymphocytes for the Treatment of CMV After Allogeneic Stem Cell Transplant: A Dose-Finding Trial
- ClinicalTrials.gov ID
- NCT00078533
- Acronym / sponsor ID
- VICTA / 12683-VICTA
- Conditions
- Cytomegalovirus Infections
- Keywords
- Allogeneic, Transplant, CMV, Stem Cell, Donor, Allogeneic stem cell recipients at risk for CMV reactivation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital Research Institute, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Apr 2004
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 2 Mar 2004 (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 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 2/3 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 and/or 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 won't 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 donor's 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CMV CTL infusion | Experimental | Biological: CMV CTL infusionSubjects are assigned a dose level at the time of enrollment. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Recipients of allogeneic donor stem cell transplants at risk for CMV reactivation with a CMV seropositive stem cell donor and at least 30 days post transplant.
- Recipients can have early evidence of CMV reactivation with greater than 2 leukocytes but less than 10 leukocytes positive for the CMV Ag per 100,000 cells.
- No evidence of graft-versus-host disease (GVHD) > Grade II at time of enrollment.
- Life expectancy > 30 days
- No severe intercurrent infections
Key exclusion criteria (5 listed)
- Patients with CMV negative stem cell donors
- Patients with GVHD Grades III-IV
- Patients receiving antiviral therapy for CMV reactivation or other viral infections such as adenovirus or herpes viruses
- Patients with significant CMV reactivation. Significant CMV reactivation is defined as one CMV Antigenemia reading with >10 leukocytes positive for the CMV Ag per 100,000 cells
- Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease
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 |
|---|---|---|
| CMV CTL infusionThree dose levels will be explored. The lowest dose level will be 1x10^7cells/m2 and the highest will be 1x10^8/m2. 3-6 pts will be entered at each dose level (depending on toxicity). If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval. Additional patients will be treated at dose level 1 in order to assess the secondary objective of virus-specific immunity from the CTL infusions | Biological | CMV CTL infusion |
Primary outcome
safety, toxicity and maximum tolerated dose (MTD)
Time frame: 30 days
Efficacy of recovery of virus-specific immunity and correlation with protection from viral reactivation/disease.
Time frame: 8 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 8 Oct 2014.
- Derived from this study: PubMed 31219185Keller MD, Darko S, Lang H, Ransier A, Lazarski CA, Wang Y, Hanley PJ, Davila BJ, Heimall JR, Ambinder RF, Barrett AJ, Rooney CM, Heslop HE, Douek DC, Bollard CM. T-cell receptor sequencing demonstrates persistence of virus-specific T cells after antiviral immunotherapy. Br J Haematol. 2019 Oct;187(2):206-218. doi: 10.1111/bjh.16053. Epub 2019 Jun 20.
- Derived from this study: PubMed 19443656Hanley PJ, Cruz CR, Savoldo B, Leen AM, Stanojevic M, Khalil M, Decker W, Molldrem JJ, Liu H, Gee AP, Rooney CM, Heslop HE, Dotti G, Brenner MK, Shpall EJ, Bollard CM. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood. 2009 Aug 27;114(9):1958-67. doi: 10.1182/blood-2009-03-213256. Epub 2009 May 14.
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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 CMV CTL infusion in people with Cytomegalovirus Infections, 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 5 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 8 Oct 2014. 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?
safety, toxicity and maximum tolerated dose (MTD) (time frame: 30 days). The study lists 2 primary outcomes in all. 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 NCT00078533, which also lists 2 linked publications.
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 8 Oct 2014.