Viral InfectionPhase 1/2ARMSNCT01570283
ARMS - Rapidly Generated Multivirus-Specific CTLs for Prophylaxis & Treatment of EBV, CMV, Adenovirus, HHV6 & BK Virus
A Phase 1/2 study testing Multivirus-specific T cells Dose Level 1, Multivirus-specific T cells Dose Level 2 and Multivirus-specific T cells Dose Level 3 in people with Viral Infection, run by AlloVir at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Viral Infection
- What is being tested?
- Multivirus-specific T cells Dose Level 1, Multivirus-specific T cells Dose Level 2 and Multivirus-specific T cells Dose Level 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2012to Sep 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients will be eligible following any type of allogeneic transplant to receive CTLs as prevention or for early reactivations as defined below.
- Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells within 12 months.
- Prevention for patients at risk of CMV, adenovirus, EBV, BK virus, or HHV6 infection
- Treatment of reactivation or infection which is defined for each virus as below
- CMV- CMV antigenemia is monitored at least weekly post transplant. Reactivation is defined at CMV antigenemia with <10 leukocytes positive or elevated PCR. If any patient develops CMV antigenemia with >10 leukocytes positive or clinical evidence of CMV infection (defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) either pre or after CTL infusions, standard treatment with Ganciclovir, and/or Foscarnet and Immunoglobulins will be initiated. Patients may receive CTLs for antigenemia or elevated PCR without visceral infection.
- Adenovirus- Adenovirus infection will be defined as the presence of adenoviral positivity as detected by PCR or culture from ONE site such as stool or blood or urine or nasopharynx.
Show all 23Show fewer
- Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture from more than two sites such as stool or blood or urine or nasopharynx.
- In patients who meet the criteria for disease Cidofovir may be added unless the subject could not tolerate this agent due to nephrotoxicity. Patients may receive CTLs for elevated PCR in blood or stool.
- EBV- EBV-LPD is defined according to recent guidelines as proven EBV-LPD defined by biopsy or probable EBV-LPD defined as an elevated EBV DNA level associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation. Patients with EBV DNA reactivation only may receive CTLs on study. Patients with proven or probable EBV-LPD should also receive Rituxan
- BK virus- Patients post transplant may develop asymptomatic BKV viruria or viremia. BK reactivation will be defined as detection of elevated BK levels by PCR in blood or urine while disease will be defined as detection in multiple sites or in one site with symptoms. Cidofovir has been administered intravenously in a low dose (i.e. up to 1 mg/kg 3 times weekly, without probenecid) or a high dose (ie, 5 mg/kg per week with probenecid) to HSCT patients with BK infections but no randomized trials are available proving its clinical efficacy. In patients who meet the criteria for disease Cidofovir may be added unless the subject could not tolerate this agent due to nephrotoxicity.
- HHV6- HHV6 reactivation will be defined as detection of elevated HHV6 levels by PCR in blood while disease will be defined as detection in multiple sites or in one site with symptoms. Ganciclovir, Cidofovir, and foscarnet have variable in vitro activity against HHV-6, and may have a role in treating HHV-6-associated disease - hence one or more of these agents will be added in patients with disease.
- Treatment may be given to eligible patients with a single or multiple infections. Patients with multiple infections with one or more reactivation and one or more controlled infection are eligible to enroll.
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone.
- Karnofsky/Lansky score of ≥ 50
- ANC greater than 500/µL.
- Bilirubin </= 2x upper limit normal
- AST </= 3 x upper limit normal
- Serum creatinine </= 2 x upper limit normal
- HgB > 8.0
- Pulse oximetry of > 90% on room air
- Available multivirus-specific CTLs
- Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
- Written informed consent and/or signed assent line from patient, parent or guardian.
Who cannot join
- Patients receiving ATG, or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
- Patients with other 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.
- Patients who have received donor lymphocyte infusion (DLI) within 28 days.
- Patients with active acute GVHD grades II-IV.
- Active and uncontrolled relapse of malignancy
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: ARMS - Administration Of Rapidly Generated Multivirus-Specific Cytotoxic T-Lymphocytes For The Prophylaxis And Treatment Of EBV, CMV, Adenovirus, HHV6, And BK Virus Infections Post Allogeneic Stem Cell Transplant
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.
Read the detailed description
To make the CTLs, subject's donors' cells were mixed with small pieces of proteins, called peptides that come from adenovirus, CMV, EBV, BKV and HHV6. These peptides stimulate donor T cells that react against the viruses to grow and train the donor T cells to kill cells that are infected with CMV, EBV, adenovirus, BKV and HHV6. Once sufficient numbers of T cells were made, they were tested to make sure they would target the cells infected with these viruses but not the normal cells. Then the cells were frozen.
When the Investigators think the subject needs them, the subject's donor's CTL cells will be thawed and injected into the intravenous line. To prevent an allergic reaction, prior to receiving the CTLs the subject may be given diphenhydramine (Benadryl) and acetaminophen (Tylenol). After the subject receives the cells, Investigators will monitor the levels of these five viruses in the blood. They will also take blood to see how long the T cells they gave the subject are lasting in the body.
If the CTL infusion has helped the subjects infection or if they have had a treatment, for example with steroid drugs that might have destroyed the T cells the subject was given, then they are allowed to receive up to 2 more doses of the cells.
The first part of this study was a dose escalation study. That means that at the beginning, patients were started on the lowest dose (1 of 3 different levels) of T cells. The next group of patients were started at a higher dose. This process continued until all 3 dose levels were studied. They would now like to enroll more patients at the highest dose level to get more information about how the T cells work.
Subjects will continue to be followed by their transplant doctors after the injection. The subject will either be seen in the clinic or they will be contacted by a research nurse to follow up for this study every week for 6 weeks then at 8 week and 3, 6 and 12 months. The subject may have other visits for their standard care. Subjects will also have regular blood tests done to follow their counts and the viral infection. To learn more about the way the T cells are working in the body, up to an extra 30-40 ml (6-8 teaspoons) of blood will be taken before the infusion and then at 1, 2, 4, 5, 6 and 8 weeks and 3 months. Blood should come from the central intravenous line, and should not require extra needle sticks.
If subjects experience a positive response or are taking medicines (such as steroids) that may affect how long T cells stay in the body, they may be able to receive up to two additional doses of the T cells at the same initial dose level from 28 days after their initial dose. After each T-cell infusion, they will be monitored as described above.
Study Duration: Subjects will be on study for approximately one year. If they receive additional doses of the T cells as described above, they will be followed until 1 year after their last dose of T-cells.
- Conditions
- Viral Infection
- Being tested
- Multivirus-specific T cells Dose Level 1, Multivirus-specific T cells Dose Level 2, Multivirus-specific T cells Dose Level 3
- Keywords
- post allogeneic hematopoietic stem cell transplant, cytotoxic T lymphocytes, Cytomegalovirus, CMV, adenovirus, Epstein-Barr virus, EBV, Human polyomavirus type I, BK virus, Human herpesvirus 6, HHV6
- Medical subject headings
- Virus Diseases, Adenoviridae Infections, Epstein-Barr Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multivirus-specific T cells Dose Level 1Biological
The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level.
Dose Level One: 5x10^6 mCTLs/m2
There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL.
Multivirus-specific T cells Dose Level 2Biological
The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level.
Dose Level Two: 1x10^7 mCTLs/m2
There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL
Multivirus-specific T cells Dose Level 3Biological
The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level.
Dose Level Three: 2x10^7 mCTLs/m2
There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL
| Study group | Role | What they receive |
|---|---|---|
| Multivirus-specific T cells 5*10^6 mCTLs/m2 for Prophylaxis | Experimental | Cohort 1 prophylaxis: Participants were administrated 5*10^6 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. Receives: Biological: Multivirus-specific T cells Dose Level 1 |
| Multivirus-specific T cells 5*10^6 mCTLs/m2 for Treatment | Experimental | Cohort 1 treatment: Participants were administrated 5*10^6 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. Receives: Biological: Multivirus-specific T cells Dose Level 1 |
| Multivirus-specific T cells 1*10^7 mCTLs/m2 for Prophylaxis | Experimental | Cohort 2 prophylaxis: Participants were administrated 1*10^7 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. Receives: Biological: Multivirus-specific T cells Dose Level 2 |
| Multivirus-specific T cells 1*10^7 mCTLs/m2 for Treatment | Experimental | Cohort 2 treatment: Participants were administrated 1*10^7 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. Receives: Biological: Multivirus-specific T cells Dose Level 2 |
| Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Prophylaxis | Experimental | Cohort 3 prophylaxis: Participants were administrated 2*10^7 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. Receives: Biological: Multivirus-specific T cells Dose Level 3 |
| Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Treatment | Experimental | Cohort 3 treatment: Participants were administrated 2*10^7 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. Receives: Biological: Multivirus-specific T cells Dose Level 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a DLT
DLT is defined as acute GvHD grades III-IV within 42 days of the last dose of CTLs, # of patients with Grade 3-5 infusion-related adverse events within 30 days of the last dose of CTLs, and # of patients with Grade 4-5 non-hematological adverse events within 30 days of the last dose of CTLs. GVHD grade III-IV scoring is based on the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) GVHD scoring stamp or equivalent. Grade 3-5 infusion-related adverse events and Grade 4-5 non-hematological adverse events are graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.X.
Measured: 42 days
Secondary outcomes (3)
Percentage of Patients Who Have a Response in Anti-viral Activity
Percentage of patients who have a response in anti-viral activity that is defined as a viral load reduction to the normal level for at least one of the five virus types
Measured: 42 days
Percentage Change of Viral Load From Baseline to Follow-up
Percentage change of viral load by PCR from baseline to follow-up. A positive number indicates a percentage decrease and a negative number indicates a percentage increase.
Measured: 3 months
Median Peak Frequency of Specific T Cells Post-infusion
Median peak frequency of specific T cells as measured by Elispot to assess reconstitution of antiviral immunity.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2012 (estimated)
- Study startSep 2012
- Primary completionAug 2016
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Viral InfectionStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- AlloVir
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Baylor College of Medicine, The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Sponsor
- Investigators
- Helen Heslop, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01570283
- Sponsor's protocol ID
- H-29966 ARMS
- Acronym
- ARMS
- Status last verified
- Apr 2019
- First submitted
- 27 Mar 2012
- Last updated
- 30 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H, Martinez C, Leung K, Carrum G, Gee AP, Vera JF, Krance RA, Brenner MK, Rooney CM, Heslop HE, Leen AM. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014 Jun 25;6(242):242ra83. doi: 10.1126/scitranslmed.3008825.
PubMed 24964991
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ARMS - Administration Of Rapidly Generated Multivirus-Specific Cytotoxic T-Lymphocytes For The Prophylaxis And Treatment Of EBV, CMV, Adenovirus, HHV6, And BK Virus Infections Post Allogeneic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT01570283
- Acronym / sponsor ID
- ARMS / H-29966 ARMS
- Conditions
- Viral Infection
- Keywords
- post allogeneic hematopoietic stem cell transplant, cytotoxic T lymphocytes, Cytomegalovirus, CMV, adenovirus, Epstein-Barr virus, EBV, Human polyomavirus type I
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- AlloVirIndustry (pharma, biotech, devices)
- Collaborators
- Baylor College of Medicine, The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Sep 2012
- Primary completion
- Aug 2016 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 4 Apr 2012 (estimated)
- Results
- Posted 30 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
To make the CTLs, subject's donors' cells were mixed with small pieces of proteins, called peptides that come from adenovirus, CMV, EBV, BKV and HHV6. These peptides stimulate donor T cells that react against the viruses to grow and train the donor T cells to kill cells that are infected with CMV, EBV, adenovirus, BKV and HHV6. Once sufficient numbers of T cells were made, they were tested to make sure they would target the cells infected with these viruses but not the normal cells. Then the cells were frozen.
When the Investigators think the subject needs them, the subject's donor's CTL cells will be thawed and injected into the intravenous line. To prevent an allergic reaction, prior to receiving the CTLs the subject may be given diphenhydramine (Benadryl) and acetaminophen (Tylenol). After the subject receives the cells, Investigators will monitor the levels of these five viruses in the blood. They will also take blood to see how long the T cells they gave the subject are lasting in the body.
If the CTL infusion has helped the subjects infection or if they have had a treatment, for example with steroid drugs that might have destroyed the T cells the subject was given, then they are allowed to receive up to 2 more doses of the cells.
The first part of this study was a dose escalation study. That means that at the beginning, patients were started on the lowest dose (1 of 3 different levels) of T cells. The next group of patients were started at a higher dose. This process continued until all 3 dose levels were studied. They would now like to enroll more patients at the highest dose level to get more information about how the T cells work.
Subjects will continue to be followed by their transplant doctors after the injection. The subject will either be seen in the clinic or they will be contacted by a research nurse to follow up for this study every week for 6 weeks then at 8 week and 3, 6 and 12 months. The subject may have other visits for their standard care. Subjects will also have regular blood tests done to follow their counts and the viral infection. To learn more about the way the T cells are working in the body, up to an extra 30-40 ml (6-8 teaspoons) of blood will be taken before the infusion and then at 1, 2, 4, 5, 6 and 8 weeks and 3 months. Blood should come from the central intravenous line, and should not require extra needle sticks.
If subjects experience a positive response or are taking medicines (such as steroids) that may affect how long T cells stay in the body, they may be able to receive up to two additional doses of the T cells at the same initial dose level from 28 days after their initial dose. After each T-cell infusion, they will be monitored as described above.
Study Duration: Subjects will be on study for approximately one year. If they receive additional doses of the T cells as described above, they will be followed until 1 year after their last dose of T-cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Multivirus-specific T cells 5*10^6 mCTLs/m2 for Prophylaxis | Experimental | Biological: Multivirus-specific T cells Dose Level 1Cohort 1 prophylaxis: Participants were administrated 5*10^6 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. |
| Multivirus-specific T cells 5*10^6 mCTLs/m2 for Treatment | Experimental | Biological: Multivirus-specific T cells Dose Level 1Cohort 1 treatment: Participants were administrated 5*10^6 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. |
| Multivirus-specific T cells 1*10^7 mCTLs/m2 for Prophylaxis | Experimental | Biological: Multivirus-specific T cells Dose Level 2Cohort 2 prophylaxis: Participants were administrated 1*10^7 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. |
| Multivirus-specific T cells 1*10^7 mCTLs/m2 for Treatment | Experimental | Biological: Multivirus-specific T cells Dose Level 2Cohort 2 treatment: Participants were administrated 1*10^7 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. |
| Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Prophylaxis | Experimental | Biological: Multivirus-specific T cells Dose Level 3Cohort 3 prophylaxis: Participants were administrated 2*10^7 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. |
| Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Treatment | Experimental | Biological: Multivirus-specific T cells Dose Level 3Cohort 3 treatment: Participants were administrated 2*10^7 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- Patients will be eligible following any type of allogeneic transplant to receive CTLs as prevention or for early reactivations as defined below.
- Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells within 12 months.
- Prevention for patients at risk of CMV, adenovirus, EBV, BK virus, or HHV6 infection
- Treatment of reactivation or infection which is defined for each virus as below
- Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture from more than two sites such as stool or blood or urine or nasopharynx.
Key exclusion criteria (6 listed)
- Patients receiving ATG, or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
- Patients with other 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.
- Patients who have received donor lymphocyte infusion (DLI) within 28 days.
- Patients with 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 |
|---|---|---|
| Multivirus-specific T cells Dose Level 1The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level. Dose Level One: 5x10^6 mCTLs/m2 There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL. | Biological | Multivirus-specific T cells 5*10^6 mCTLs/m2 for Prophylaxis, Multivirus-specific T cells 5*10^6 mCTLs/m2 for Treatment |
| Multivirus-specific T cells Dose Level 2The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level. Dose Level Two: 1x10^7 mCTLs/m2 There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL | Biological | Multivirus-specific T cells 1*10^7 mCTLs/m2 for Prophylaxis, Multivirus-specific T cells 1*10^7 mCTLs/m2 for Treatment |
| Multivirus-specific T cells Dose Level 3The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level. Dose Level Three: 2x10^7 mCTLs/m2 There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL | Biological | Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Prophylaxis, Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Treatment |
Primary outcome
Number of Participants With a DLT
Time frame: 42 days
DLT is defined as acute GvHD grades III-IV within 42 days of the last dose of CTLs, # of patients with Grade 3-5 infusion-related adverse events within 30 days of the last dose of CTLs, and # of patients with Grade 4-5 non-hematological adverse events within 30 days of the last dose of CTLs. GVHD grade III-IV scoring is based on the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) GVHD scoring stamp or equivalent. Grade 3-5 infusion-related adverse events and Grade 4-5 non-hematological adverse events are graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.X.
3 secondary outcomes
Percentage of Patients Who Have a Response in Anti-viral Activity
Time frame: 42 days
Percentage Change of Viral Load From Baseline to Follow-up
Time frame: 3 months
Median Peak Frequency of Specific T Cells Post-infusion
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24964991Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H, Martinez C, Leung K, Carrum G, Gee AP, Vera JF, Krance RA, Brenner MK, Rooney CM, Heslop HE, Leen AM. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014 Jun 25;6(242):242ra83. doi: 10.1126/scitranslmed.3008825.
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International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 (IntReALL BCP 2020)
B-Cell Acute Lymphoblastic Leukaemia
RecruitingPhase 3
A Study of Secutrelvir in Participants With Coronavirus Disease 2019 (COVID-19) Who Are at High Risk for Progression to Severe Disease
SARS-CoV-2
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 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 1/2 study testing Multivirus-specific T cells Dose Level 1, Multivirus-specific T cells Dose Level 2 and Multivirus-specific T cells Dose Level 3 in people with Viral Infection, run by AlloVir 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 6 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 30 May 2019. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With a DLT (time frame: 42 days). 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 NCT01570283, which also lists 1 linked publication.
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 30 May 2019.