EBV InfectionEAP CHALLAHNCT01945619
Allogeneic Virus-Specific Cytotoxic T-Lymphocytes(CTL), Persistent/Recurrent Viral Infection Post-HSCT (EAP CHALLAH)
A study testing Trivirus-Specific CTLs in people with EBV Infection and CMV Infection, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Subjects have a type of blood cell cancer, other blood disease or a genetic disease for which they received a stem cell transplant. After transplant while the immune system grows back the subjects have an infection with one or more of three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) or adenovirus - that… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- EBV Infection, CMV Infection, Adenoviral Infection
- What is being tested?
- Trivirus-Specific CTLs
- Type of treatment
- Injection or infusion
- How many people
- Not given
- Where
- 2 sitesUnited States
- Study dates
- Start not givento not given
- Phase
- Expanded access
- 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
- Child, Adult, Older adult
Who may be able to join
- Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or single or double umbilical cord blood.
- CMV, adenovirus or EBV infection persistent despite standard therapy
- For CMV infection
- Patients with CMV disease: defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates OR
- Failure of antiviral therapy: defined as the continued presence of pp65 antigenemia (>1+ cell/100,000 cells) or DNAemia (as defined by reference lab performing PCR assay but usually >400 copies/ml) after at least 7 days of antiviral therapy OR
- Relapse after antiviral therapy defined as recurrence of either pp65 antigenemia or DNAemia after at least 2 weeks of antiviral therapy
Show all 23Show fewer
- For CMV infection, standard therapy is defined as 7 days therapy with Ganciclovir, Foscarnet or Cidofovir for patients with disease or recurrence after 14 days therapy
- For EBV infection
- EBV infection is defined as:
- Biopsy proven lymphoma with EBV genomes detected in tumor cells by immunocytochemistry or in situ PCR OR
- Or clinical or imaging findings consistent with EBV lymphoma and elevated EBV viral load in peripheral blood.
- For EBV infection, standard therapy is defined as rituximab given at 375mg/m2 in patients for 1-4 doses with a CD20+ve tumor
- Failure is defined as
- There was an increase or less than 50% response at sites of disease for EBV lymphoma OR
- There was a rise or a fall of less than 50% in EBV viral load in peripheral blood or any site of disease
- For adenovirus infection or disease
- Adenovirus infection is defined as the presence of adenoviral positivity as detected by PCR, DAA or culture from ONE site such as stool or blood or urine or nasopharynx OR
- Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture from two or more sites such as stool or blood or urine or nasopharynx
- Standard therapy is defined as 7 days therapy with Cidofovir (if renal function permits this agent to be given).
- Failure is defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease as measured by PCR or any other quantitative assay).
- Patients with multiple CMV, EBV or Adenovirus infections are eligible given that each infection is persistent despite standard therapy as defined above. Patients with multiple infections with one persistent infection and one controlled infection are eligible to enroll.
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone.
- Written informed consent and/or signed assent line from patient, parent or guardian.
Who cannot join
- Received ATG, or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
- Uncontrolled infections. 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.
- Received donor lymphocyte infusion (DLI) within 28 days.
- Active acute GVHD grades II-IV.
- Active and uncontrolled relapse of malignancy
- Pregnant or lactating in female patients, if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
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: Expanded Access Protocol: Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation or Infection With Adenovirus, CMV and EBV After HSCT
Subjects have a type of blood cell cancer, other blood disease or a genetic disease for which they received a stem cell transplant. After transplant while the immune system grows back the subjects have an infection with one or more of three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) or adenovirus - that has persisted or come back despite standard therapy.
Adenovirus is a virus that causes symptoms of a common cold normally but can cause serious life-threatening infections in patients who have weak immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the gut, the liver, the pancreas and the eyes.
Read more
CMV is a virus that can also 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 subject and/or the subject's donor are positive for CMV, s/he is at risk of developing CMV disease while his/her immune system is weak post transplant.
EBV is the virus that causes glandular fever or kissing disease. It is also normally controlled by a healthy immune system, but when the immune system is weak, it can cause fevers, enlarged lymph nodes and sometimes develop into a type of cancer called lymphoma.
This treatment with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from the transplant donor. However, as it takes 2-3 months to make the cells, that approach is not practical when the subject already has an infection. We want to find out if we can use CTLs which have already been made from another donor that match the subject and his/her donor as closely as possible and if the CTLs will last in the body and have activity against these viruses.
In a recent study these cells were given to 50 patients with viral infections post transplant and over 70% had a complete or partial response. The purpose of this study is to make CTL lines leftover from that previous study available to patients with viral infections that have not responded to standard treatments.
These virus-specific CTLs are an investigational product not approved by the FDA.
Read the detailed description
The CTL lines were made at Baylor College of Medicine from donors for other transplant patients or other normal donors from the National Marrow Donor Program. All donors were screened in the same way as 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 infected a type of blood cells called monocytes with a specially produced adenovirus gene that also carries part of the CMV gene. The monocytes with these new genes then stimulated the T cells. This stimulation trained the T cells to kill cells with this part of the CMV virus or with adenovirus.
We then grew these CTLs with more stimulation with EBV infected cells (which we made from donor blood by infecting them with EBV in the laboratory). We also put the adenovirus that carries the CMV gene into these EBV infected cells so that they too had CMV and adenovirus proteins. These EBV infected cells were treated with radiation so they cannot grow. By this type of culture, we grew out T cells that can see and attack cells infected with EBV, adenovirus or CMV. Once we made sufficient numbers of T cells we tested them to make sure they killed cells infected with these viruses and then froze them.
The cells will be thawed and injected into an intravenous line over 1-5 minutes.
All participants on this study will get the same dose of cells. However if the subject's infection responds to the CTLs, s/he may be offered up to 4 more doses at two-week intervals. If the infection does not respond, the doctors may also try a line from a different donor.
- Conditions
- EBV Infection, CMV Infection, Adenoviral Infection
- Being tested
- Trivirus-Specific CTLs
- Keywords
- CMV, Adenovirus, EBV, Stem cell transplant, cytotoxic T-lymphocytes
- Medical subject headings
- Epstein-Barr Virus Infections, Cytomegalovirus Infections, Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trivirus-Specific CTLsBiological
Patients will receive up to 2 x 10^7 CHM-CTL/m2 as a single infusion and may receive up to 4 additional infusions at intervals of at least 2 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EBV 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
- Expanded access
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, Children's Hospital Los Angeles, Duke University, Hackensack Meridian Health, New York Medical College, University of Texas Southwestern Medical Center, Children's National Research Institute, Johns Hopkins All Children's Hospital
- 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
- NCT01945619
- Sponsor's protocol ID
- H-31634, EAP CHALLAH
- Other IDs
- EAP CHALLAH
- Acronym
- EAP CHALLAH
- Status last verified
- Jan 2016
- First submitted
- 16 Sep 2013
- Last updated
- 21 Jan 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expanded Access Protocol: Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation or Infection With Adenovirus, CMV and EBV After HSCT
- ClinicalTrials.gov ID
- NCT01945619
- Acronym / sponsor ID
- EAP CHALLAH / H-31634, EAP CHALLAH
- Conditions
- EBV Infection, CMV Infection, Adenoviral Infection
- Keywords
- CMV, Adenovirus, EBV, Stem cell transplant, cytotoxic T-lymphocytes
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- 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, Children's Hospital Los Angeles, Duke University, Hackensack Meridian Health, New York Medical College, University of Texas Southwestern Medical Center, Children's National Research Institute, Johns Hopkins All Children's Hospital
- First posted
- 18 Sep 2013 (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.
Subjects have a type of blood cell cancer, other blood disease or a genetic disease for which they received a stem cell transplant. After transplant while the immune system grows back the subjects have an infection with one or more of three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) or adenovirus - that has persisted or come back despite standard therapy.
Adenovirus is a virus that causes symptoms of a common cold normally but can cause serious life-threatening infections in patients who have weak immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the gut, the liver, the pancreas and the eyes.
CMV is a virus that can also 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 subject and/or the subject's donor are positive for CMV, s/he is at risk of developing CMV disease while his/her immune system is weak post transplant.
EBV is the virus that causes glandular fever or kissing disease. It is also normally controlled by a healthy immune system, but when the immune system is weak, it can cause fevers, enlarged lymph nodes and sometimes develop into a type of cancer called lymphoma.
This treatment with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from the transplant donor. However, as it takes 2-3 months to make the cells, that approach is not practical when the subject already has an infection. We want to find out if we can use CTLs which have already been made from another donor that match the subject and his/her donor as closely as possible and if the CTLs will last in the body and have activity against these viruses.
In a recent study these cells were given to 50 patients with viral infections post transplant and over 70% had a complete or partial response. The purpose of this study is to make CTL lines leftover from that previous study available to patients with viral infections that have not responded to standard treatments.
These virus-specific CTLs are an investigational product not approved by the FDA.
Detailed description
The CTL lines were made at Baylor College of Medicine from donors for other transplant patients or other normal donors from the National Marrow Donor Program. All donors were screened in the same way as 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 infected a type of blood cells called monocytes with a specially produced adenovirus gene that also carries part of the CMV gene. The monocytes with these new genes then stimulated the T cells. This stimulation trained the T cells to kill cells with this part of the CMV virus or with adenovirus.
We then grew these CTLs with more stimulation with EBV infected cells (which we made from donor blood by infecting them with EBV in the laboratory). We also put the adenovirus that carries the CMV gene into these EBV infected cells so that they too had CMV and adenovirus proteins. These EBV infected cells were treated with radiation so they cannot grow. By this type of culture, we grew out T cells that can see and attack cells infected with EBV, adenovirus or CMV. Once we made sufficient numbers of T cells we tested them to make sure they killed cells infected with these viruses and then froze them.
The cells will be thawed and injected into an intravenous line over 1-5 minutes.
All participants on this study will get the same dose of cells. However if the subject's infection responds to the CTLs, s/he may be offered up to 4 more doses at two-week intervals. If the infection does not respond, the doctors may also try a line from a different donor.
Study design
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or single or double umbilical cord blood.
- CMV, adenovirus or EBV infection persistent despite standard therapy
- Patients with multiple CMV, EBV or Adenovirus infections are eligible given that each infection is persistent despite standard therapy as defined above. Patients with multiple infections with one persistent infection and one controlled infection are eligible to enroll.
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone.
- Written informed consent and/or signed assent line from patient, parent or guardian.
Key exclusion criteria (7 listed)
- Received ATG, or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
- Uncontrolled infections. 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.
- Received donor lymphocyte infusion (DLI) within 28 days.
- Active acute GVHD grades II-IV.
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 |
|---|---|---|
| Trivirus-Specific CTLsPatients will receive up to 2 x 10^7 CHM-CTL/m2 as a single infusion and may receive up to 4 additional infusions at intervals of at least 2 weeks. | Biological | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2016.
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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 study testing Trivirus-Specific CTLs in people with EBV Infection and CMV 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 23 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 21 Jan 2016. 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.
Are results available for this study?
Results are not available in the source record.
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.
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 21 Jan 2016.