Cytomegalovirus InfectionPhase 1ACT-CATNCT00880789
Safety, Toxicity and MTD of One Intravenous IV Injection of Donor CTLs Specific for CMV and Adenovirus
A Phase 1 study testing CMV/AdV specific T cells in people with Cytomegalovirus Infection and Adenovirus Infection, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
With this study, we want to see if we can use a kind of white blood cell called T cells to prevent or treat AdV and CMV infection. We will grow these T cells from the cord blood before the patients transplant. Read more about this study
- Who is it for?
- Ages Up to 90 years
- Conditions the study is for
- Cytomegalovirus Infection, Adenovirus Infection
- What is being tested?
- CMV/AdV specific T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2009to Jun 2014
- 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 Up to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient with malignant or nonmalignant diseases who are candidates for transplant.
- Patients must have a single CB unit matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit must be cryopreserved in two fractions, with a minimum of 2.5x10^7 total nucleated cells per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below.
- Recipients of a single cord blood unit fractionated into 2 fractions (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral disease or reactivation.
- Lansky/Karnofsky scores 60 or greater
- Absolute neutrophil count (ANC) greater than 500/ul.
- No evidence of GVHD > Grade II at time of enrollment.
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- Life expectancy > 30 days
- Absence of severe renal disease (Creatinine > x 3 normal for age)
- Absence of severe hepatic disease. Direct bilirubin must be less than 3 mg/dl and AST less than 5x upper limit of normal
- Patient must be at least 30 days post transplant to be eligible to receive CTL
- Written informed consent and/or signed assent line from patient, parent or guardian.
- Patient not on Fi02 of >60%
Who cannot join
- Pregnant or Lactating
- Patients with active central nervous system disease
- Patients with Karnofsky performance status <70%
- Patients with grade 3 or 4 or primary myelofibrosis
- Patients with suitable related donors
- Pregnant or lactating
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- Unable to wean steroids to 0.5 mg/kg/day or less prednisone.
- Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia in absence of PTLD). For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- 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: Adoptive Transfer of Cord Blood T Cells To Prevent and Treat CMV and Adenovirus Infections After Transplantation
With this study, we want to see if we can use a kind of white blood cell called T cells to prevent or treat AdV and CMV infection. We will grow these T cells from the cord blood before the patients transplant. These cells have been trained to attack adenovirus/CMV-infected cells and are called Adenoviral/CMV-specific cytotoxic (killer) T-cells or "AdV/CMV-CTL." We would plan to give the patient one dose of AdV/CMV-CTL any time from 30 days after their transplant. We have used T cells made in this way from the blood of donors to prevent infections in patients who are getting a bone marrow or blood stem cell transplant but this will be the first time we make them from cord blood.
Read the detailed description
We plan to grow T cells from the cord blood in the laboratory in a special way, to see if they can help prevent or treat infections in transplant patients with these viruses. This therapy with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from donor blood and given to patients receiving bone marrow or blood stem cell transplants. We want to find out if we can use CTLs that we will make from cord blood to prevent or treat viral infections when the patient's immunity is weak after receiving the cord blood transplant. These cells are called "CMV/AdV specific CTLs" because they can attack those two viruses.
The doctor will already have found a cord blood unit that is suitable for the patient's transplant. If the patient agrees to this study we will take 5-10 ml (1-2 teaspoons) from this cord blood unit before the transplant. We will only take as much cord blood as is available in a specially frozen small fraction of the cord blood unit.
We will use this cord blood to grow T cells in the lab. From this blood we will first grow special type of cells called dendritic cells and we will put a specially produced human virus (adenovirus) that carries the CMVpp65 gene into these dendritic cells. The dendritic cells will be irradiated so they cannot grow and then used to stimulate the T cells. This stimulation will train the T cells to kill cells with CMV and adenovirus on their surface.
We will then grow large numbers of these AdV/CMV-specific CTLs by more stimulation with EBV infected B cells (which we will make from the cord blood by infecting them with EBV in the laboratory). We will also put the special virus into these B cells so that they too have AdV/CMV. Again, these B cells will be treated with radiation so they cannot grow. Once we have made enough T cells we will test them to make sure they kill cells infected with Adenovirus and CMV. To make sure that these cells won't attack the patient's own healthy tissues, we test these cells against some of the blood cells that we will grow in the laboratory. These will be used to check to see if the AdV/CMV CTL can attack them. Alternatively, we may take blood from a first degree relative or take a small piece of skin from the patient to grow skin cells, which can also to be used to check if AdV/CMV CTL can attack them. The skin biopsy can be done at the same time as another procedure such as a bone marrow biopsy.
The cord donor's AdV/CMV CTL cells will be thawed and injected into the IV line over a period of up to 10 minutes.Patients may be premedicated with Benadryl and Tylenol. If the patient agrees and if he/she is well enough, one dose of CTL will be given on or after day 30 following transplant. If the patient does not have AdV/CMV infection we will not give antiviral medications to them during this study but we will monitor the patient closely to check for AdV/CMV infection. If the patient does have AdV/CMV infection before CTL infusion they may also be treated with antiviral medications during this study. We will monitor the patients closely for AdV/CMV infection by collecting blood and possibly urine and stool and testing them for AdV/CMV.
- Conditions
- Cytomegalovirus Infection, Adenovirus Infection
- Being tested
- CMV/AdV specific T cells
- Keywords
- Cord Blood Transplant, cytomegalovirus, CMV, Adenovirus, ADV
- Medical subject headings
- Cytomegalovirus Infections, Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV/AdV specific T cellsBiological
CTL Dose Given from Day +30 post SCT (stem cell transplant). For the trial, two patients are allocated in each cohort and are followed for 30 days post IV injection of transduced T-cells for evaluation of DLTs. A maximum 18 patients will be accrued into each group. The final MTD will be the dose with probability closest to the target toxicity rate at these termination points. The trial continues until a minimum of 12 patients have been treated. The trial will stop when the maximum 18 patients have been treated, or when six patients have been treated at the current MTD. We therefore expect to enroll between 12-18 patients into this trial.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level One: 5x10^6/m2 | Experimental | CTL Dose Given from Day +30 post SCT (stem cell transplant). For the trial, two patients are allocated in each cohort and are followed for 30 days post IV injection of transduced T-cells for evaluation of DLTs. A maximum 18 patients will be accrued into each group. The final MTD will be the dose with probability closest to the target toxicity rate at these termination points. The trial continues until a minimum of 12 patients have been treated. The trial will stop when the maximum 18 patients have been treated, or when six patients have been treated at the current MTD. We therefore expect to enroll between 12-18 patients into this trial. Receives: Biological: CMV/AdV specific T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine safety, toxicity and MTD of one intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV and Adenovirus given to patients with or at risk for CMV and adenovirus disease after cord blood transplant
Measured: 1 year
Secondary outcomes (3)
To evaluate the feasibility of generating a sufficient number of umbilical cord blood-derived cytotoxic T lymphocytes (CTLs) specific for CMV and Adenovirus
Measured: 1 year
To evaluate the impact of these CTLs on Adenovirus-specific T-lymphocyte immune reconstitution.
Measured: 1 year
To evaluate the recovery of virus-specific immunity after CTL infusion and its correlation with viral clearance and/or protection from viral infection/disease.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionAug 2013
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionStudies 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
- 9 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, Caridad Martinez, Baylor College of Medicine
- Investigators
- Caridad A. Martinez, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00880789
- Sponsor's protocol ID
- 23668-ACT CAT
- Acronym
- ACT-CAT
- Status last verified
- Oct 2014
- First submitted
- 13 Apr 2009
- Last updated
- 15 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Transfer of Cord Blood T Cells To Prevent and Treat CMV and Adenovirus Infections After Transplantation
- ClinicalTrials.gov ID
- NCT00880789
- Acronym / sponsor ID
- ACT-CAT / 23668-ACT CAT
- Conditions
- Cytomegalovirus Infection, Adenovirus Infection
- Keywords
- Cord Blood Transplant, cytomegalovirus, CMV, Adenovirus, ADV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 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
- May 2009
- Primary completion
- Aug 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 14 Apr 2009 (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.
With this study, we want to see if we can use a kind of white blood cell called T cells to prevent or treat AdV and CMV infection. We will grow these T cells from the cord blood before the patients transplant. These cells have been trained to attack adenovirus/CMV-infected cells and are called Adenoviral/CMV-specific cytotoxic (killer) T-cells or "AdV/CMV-CTL." We would plan to give the patient one dose of AdV/CMV-CTL any time from 30 days after their transplant. We have used T cells made in this way from the blood of donors to prevent infections in patients who are getting a bone marrow or blood stem cell transplant but this will be the first time we make them from cord blood.
Detailed description
We plan to grow T cells from the cord blood in the laboratory in a special way, to see if they can help prevent or treat infections in transplant patients with these viruses. This therapy with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from donor blood and given to patients receiving bone marrow or blood stem cell transplants. We want to find out if we can use CTLs that we will make from cord blood to prevent or treat viral infections when the patient's immunity is weak after receiving the cord blood transplant. These cells are called "CMV/AdV specific CTLs" because they can attack those two viruses.
The doctor will already have found a cord blood unit that is suitable for the patient's transplant. If the patient agrees to this study we will take 5-10 ml (1-2 teaspoons) from this cord blood unit before the transplant. We will only take as much cord blood as is available in a specially frozen small fraction of the cord blood unit.
We will use this cord blood to grow T cells in the lab. From this blood we will first grow special type of cells called dendritic cells and we will put a specially produced human virus (adenovirus) that carries the CMVpp65 gene into these dendritic cells. The dendritic cells will be irradiated so they cannot grow and then used to stimulate the T cells. This stimulation will train the T cells to kill cells with CMV and adenovirus on their surface.
We will then grow large numbers of these AdV/CMV-specific CTLs by more stimulation with EBV infected B cells (which we will make from the cord blood by infecting them with EBV in the laboratory). We will also put the special virus into these B cells so that they too have AdV/CMV. Again, these B cells will be treated with radiation so they cannot grow. Once we have made enough T cells we will test them to make sure they kill cells infected with Adenovirus and CMV. To make sure that these cells won't attack the patient's own healthy tissues, we test these cells against some of the blood cells that we will grow in the laboratory. These will be used to check to see if the AdV/CMV CTL can attack them. Alternatively, we may take blood from a first degree relative or take a small piece of skin from the patient to grow skin cells, which can also to be used to check if AdV/CMV CTL can attack them. The skin biopsy can be done at the same time as another procedure such as a bone marrow biopsy.
The cord donor's AdV/CMV CTL cells will be thawed and injected into the IV line over a period of up to 10 minutes.Patients may be premedicated with Benadryl and Tylenol. If the patient agrees and if he/she is well enough, one dose of CTL will be given on or after day 30 following transplant. If the patient does not have AdV/CMV infection we will not give antiviral medications to them during this study but we will monitor the patient closely to check for AdV/CMV infection. If the patient does have AdV/CMV infection before CTL infusion they may also be treated with antiviral medications during this study. We will monitor the patients closely for AdV/CMV infection by collecting blood and possibly urine and stool and testing them for AdV/CMV.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Level One: 5x10^6/m2 | Experimental | Biological: CMV/AdV specific T cellsCTL Dose Given from Day +30 post SCT (stem cell transplant). For the trial, two patients are allocated in each cohort and are followed for 30 days post IV injection of transduced T-cells for evaluation of DLTs. A maximum 18 patients will be accrued into each group. The final MTD will be the dose with probability closest to the target toxicity rate at these termination points. The trial continues until a minimum of 12 patients have been treated. The trial will stop when the maximum 18 patients have been treated, or when six patients have been treated at the current MTD. We therefore expect to enroll between 12-18 patients into this trial. |
Who may qualify
- Ages
- Up to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Patient with malignant or nonmalignant diseases who are candidates for transplant.
- Patients must have a single CB unit matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit must be cryopreserved in two fractions, with a minimum of 2.5x10^7 total nucleated cells per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below.
- Recipients of a single cord blood unit fractionated into 2 fractions (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral disease or reactivation.
- Lansky/Karnofsky scores 60 or greater
- Absolute neutrophil count (ANC) greater than 500/ul.
Key exclusion criteria (9 listed)
- Pregnant or Lactating
- Patients with active central nervous system disease
- Patients with Karnofsky performance status <70%
- Patients with grade 3 or 4 or primary myelofibrosis
- Patients with suitable related donors
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/AdV specific T cellsCTL Dose Given from Day +30 post SCT (stem cell transplant). For the trial, two patients are allocated in each cohort and are followed for 30 days post IV injection of transduced T-cells for evaluation of DLTs. A maximum 18 patients will be accrued into each group. The final MTD will be the dose with probability closest to the target toxicity rate at these termination points. The trial continues until a minimum of 12 patients have been treated. The trial will stop when the maximum 18 patients have been treated, or when six patients have been treated at the current MTD. We therefore expect to enroll between 12-18 patients into this trial. | Biological | Dose Level One: 5x10^6/m2 |
Primary outcome
To determine safety, toxicity and MTD of one intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV and Adenovirus given to patients with or at risk for CMV and adenovirus disease after cord blood transplant
Time frame: 1 year
3 secondary outcomes
To evaluate the feasibility of generating a sufficient number of umbilical cord blood-derived cytotoxic T lymphocytes (CTLs) specific for CMV and Adenovirus
Time frame: 1 year
To evaluate the impact of these CTLs on Adenovirus-specific T-lymphocyte immune reconstitution.
Time frame: 1 year
To evaluate the recovery of virus-specific immunity after CTL infusion and its correlation with viral clearance and/or protection from viral infection/disease.
Time frame: 1 year
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 15 Oct 2014.
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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.
Caridad A. Martinez, 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/AdV specific T cells in people with Cytomegalovirus Infection and Adenovirus Infection, 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 12 inclusion and 9 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 15 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?
To determine safety, toxicity and MTD of one intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV and Adenovirus given to patients with or at risk for CMV and adenovirus disease after cord blood transplant (time frame: 1 year). 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 15 Oct 2014.