BK Virus InfectionPhase 1NCT02313844
Most Closely Human Leukocyte Antigen (HLA)-Matched BK Virus-specific T Lymphocytes (Viralym-B)
A Phase 1 study testing Viralym-B in people with BK Virus Infection, run by AlloVir at 2 sites in United States.
Trial summary
Patients enrolled on this study will have received a stem cell transplant. After a transplant, while the immune system grows back the patient is at risk for infection. Some viruses can stay in the body for life, and if the immune system is weakened (like after a transplant), they can cause life-threatening infections. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- BK Virus Infection
- What is being tested?
- Viralym-B
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Mar 2018to Dec 2019
- 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
- Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells or single or double cord blood within 24 months.
- Persistent or recurrent BK virus infection or disease despite at least 7 days of standard therapy or failure of therapy as described below or if unable to tolerate standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function.
- BK virus infection: defined as the presence of BK virus positivity as detected by Polymerase chain reaction (PCR) or culture in one site such as blood or urine.
- BK virus disease: defined as presence of BK virus detectable by culture or PCR in blood or urine or other body fluids and symptoms of disease including but not limited to persistent microscopic and macroscopic hematuria or detectable BK virus in more than one site.
- Failure of therapy: 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) after 7 days of antiviral therapy.
- Clinical status at enrollment to allow tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent).
Show all 12Show fewer
- Hemoglobin (HgB)>8.0 (may be transfused)
- Received transplant care locally and will remain in the Houston area for at least 6 weeks post Viralym B infusion
- Pulse oximetry of > 90% on room air
- Available Viralym-B T cell line
- Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
Who cannot join
- Patients receiving (Anti-thymocyte globulin) ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of treatment with Viralym-B
- Patients with other uncontrolled/progressing infections defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. 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. 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 of Viralym-B infusion.
- Patients who have received other investigational drugs within 28 days of Viralym-B infusion
- Patients with active acute Graft versus host disease (GVHD) grades II-IV.
- Active and uncontrolled relapse of malignancy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Childrens Hospital
Houston, Texas, 77030
The Methodist Hospital system
Houston, Texas, 77030
About this study
Official title: A Phase I Study Using Most Closely HLA-matched BK Virus-specific T Lymphocytes for the Treatment of BK Virus Infections Post-allogeneic Stem Cell Transplant(VIRALYM-B)
Patients enrolled on this study will have received a stem cell transplant. After a transplant, while the immune system grows back the patient is at risk for infection. Some viruses can stay in the body for life, and if the immune system is weakened (like after a transplant), they can cause life-threatening infections.
BK virus (BKV) is a virus that can cause serious life-threatening infections in patients who have weak immune systems. It affects the urinary tract, and can cause frequent urination, blood in the urine, and severe pain.
Read more
Investigators want to see if they can use a kind of white blood cell called T cells to treat BKV infections that occur after a transplant. Investigators have observed in other studies that treatment with specially trained T cells has been successful when the cells are made from the transplant donor. However as it takes 1-2 months to make the cells, that approach is not practical when a patient already has an infection.
Investigators have now generated BKV-specific T cells from the blood of healthy donors and created a bank of these cells. Investigators have previously successfully used frozen virus-specific T cell lines generated from healthy donors to treat virus infections after bone marrow transplant, and have now improved the production method and customized the bank of lines to specifically and exclusively target BKV.
In this study, investigators want to find out if the banked BKV-specific T cells derived from healthy donors are safe and can help to treat BK virus infection.
The BKV-specific T cells (Viralym-B) are an investigational product not approved by the Food and Drug Administration (FDA).
Read the detailed description
To make BKV-specific T cells (Viralym-B cells), small pieces of protein called peptides that come from BKV were mixed with blood cells from healthy donors. These peptides train a kind of white blood cell called T cells to recognize and kill cells that are infected with BKV. These T cells were then grown in special growth factors in special flasks in the lab. Once we made sufficient numbers of cells, we tested them to make sure they recognized cells infected by BK virus, and then we froze them.
When we think the subject needs them, Viralym-B cells will be thawed and injected into the intravenous line. To prevent an allergic reaction, prior to receiving Viralym-B cells the subject may be given diphenhydramine (Benadryl) and acetaminophen (Tylenol). The subject will remain in the clinic for at least one hour after the infusion. After the subject receives the cells, the transplant doctor will monitor the levels of BK virus in the blood. We will also take blood to see how long the cells we gave the subject are lasting in the body.
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 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 as part of their standard care.
To learn more about the way Viralym-B cells are working in the body, an extra 30-40 ml (6-8 teaspoons) of blood will be taken before the infusion and then at study follow-up visits at 1, 2, 3, 4 and 6 weeks, and 3 months after the infusion. Blood should come from the central intravenous line, and should not require extra needle sticks.
All participants on this study will be infused with the same number (dose) of cells. If Viralym-B 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 4 additional infusions of the Viralym-B cells at the same initial dose level from 28 days after their initial infusion. Following infusions should be at least 14 days apart. After each Viralym-B cells infusion, subjects will be monitored as described above.
- Conditions
- BK Virus Infection
- Being tested
- Viralym-B
- Keywords
- BK virus, Virus specific T cells, Viral infections
- Medical subject headings
- Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Viralym-BBiological
Follow-up Assessments: The timing of follow-up visits is based on the date of Viralym-B infusion. If a patient has multiple Viralym-B infusions the schedule resets again at the beginning so follow up relates to the last Viralym-B infusion.
Follow up will occur at 7 days, 14 days, 21 days, 28 days, 42 days, 90 days, 180 days, and 365 days post enrollment.
| Study group | Role | What they receive |
|---|---|---|
| Viralym-B | Experimental | Partially HLA-matched Viralym-B cells will be thawed and given by intravenous injection. Patients will receive 2 x 10^7 partially HLA-matched Viralym-B/m2 as a single infusion.
If a patient has a partial response they are eligible to receive up to 4 additional doses at biweekly intervals. These doses would come from the original infused line if sufficient vials were available but may come from another line if there are insufficient cells in the original line. Receives: Biological: Viralym-B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of patients with adverse events after Viralym-B infusion
To determine if administration of banked BKV-specific T cells (Viralym-B) derived from healthy donors are safe in patients with BKV infection after allogeneic stem cell transplant.
Measured: 42 days
Secondary outcomes (2)
Assessment of BK viral load response to the Viralym-B infusion
Viral load over time within a patient will be visualized to reveal the temporal patterns of immune response. Plots of smooth curves will be generated for each patient to graphically illustrate the pattern and duration of T-cell changes.
Measured: 1 year
Reconstitution of antiviral immunity after Viralym-B infusion
Reconstitution of antiviral immunity over time within a patient will be visualized to reveal the temporal patterns of immune response. Plots of smooth curves will be generated for each patient to graphically illustrate the pattern and duration of T-cell changes.
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 posted10 Dec 2014 (estimated)
- Study start1 Mar 2018 (estimated)
- Primary completionJun 2019 (estimated)
- Study completionDec 2019 (estimated)
Why it stopped: Not developing product
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 BK Virus 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- AlloVir
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Swati Naik, MD, Principal investigator, Texas Childrens HospitalBilal Omer, MD, Principal investigator, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02313844
- Sponsor's protocol ID
- H35885 Viralym-B
- Status last verified
- Apr 2018
- First submitted
- 8 Dec 2014
- Last updated
- 9 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Leen AM, Bollard CM, Mendizabal AM, Shpall EJ, Szabolcs P, Antin JH, Kapoor N, Pai SY, Rowley SD, Kebriaei P, Dey BR, Grilley BJ, Gee AP, Brenner MK, Rooney CM, Heslop HE. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013 Jun 27;121(26):5113-23. doi: 10.1182/blood-2013-02-486324. Epub 2013 Apr 22.
PubMed 23610374Papadopoulou 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 9 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Using Most Closely HLA-matched BK Virus-specific T Lymphocytes for the Treatment of BK Virus Infections Post-allogeneic Stem Cell Transplant(VIRALYM-B)
- ClinicalTrials.gov ID
- NCT02313844
- Acronym / sponsor ID
- H35885 Viralym-B
- Conditions
- BK Virus Infection
- Keywords
- BK virus, Virus specific T cells, Viral infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not developing product
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AlloVirIndustry (pharma, biotech, devices)
- Study start
- 1 Mar 2018 (estimated)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 10 Dec 2014 (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 enrolled on this study will have received a stem cell transplant. After a transplant, while the immune system grows back the patient is at risk for infection. Some viruses can stay in the body for life, and if the immune system is weakened (like after a transplant), they can cause life-threatening infections.
BK virus (BKV) is a virus that can cause serious life-threatening infections in patients who have weak immune systems. It affects the urinary tract, and can cause frequent urination, blood in the urine, and severe pain.
Investigators want to see if they can use a kind of white blood cell called T cells to treat BKV infections that occur after a transplant. Investigators have observed in other studies that treatment with specially trained T cells has been successful when the cells are made from the transplant donor. However as it takes 1-2 months to make the cells, that approach is not practical when a patient already has an infection.
Investigators have now generated BKV-specific T cells from the blood of healthy donors and created a bank of these cells. Investigators have previously successfully used frozen virus-specific T cell lines generated from healthy donors to treat virus infections after bone marrow transplant, and have now improved the production method and customized the bank of lines to specifically and exclusively target BKV.
In this study, investigators want to find out if the banked BKV-specific T cells derived from healthy donors are safe and can help to treat BK virus infection.
The BKV-specific T cells (Viralym-B) are an investigational product not approved by the Food and Drug Administration (FDA).
Detailed description
To make BKV-specific T cells (Viralym-B cells), small pieces of protein called peptides that come from BKV were mixed with blood cells from healthy donors. These peptides train a kind of white blood cell called T cells to recognize and kill cells that are infected with BKV. These T cells were then grown in special growth factors in special flasks in the lab. Once we made sufficient numbers of cells, we tested them to make sure they recognized cells infected by BK virus, and then we froze them.
When we think the subject needs them, Viralym-B cells will be thawed and injected into the intravenous line. To prevent an allergic reaction, prior to receiving Viralym-B cells the subject may be given diphenhydramine (Benadryl) and acetaminophen (Tylenol). The subject will remain in the clinic for at least one hour after the infusion. After the subject receives the cells, the transplant doctor will monitor the levels of BK virus in the blood. We will also take blood to see how long the cells we gave the subject are lasting in the body.
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 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 as part of their standard care.
To learn more about the way Viralym-B cells are working in the body, an extra 30-40 ml (6-8 teaspoons) of blood will be taken before the infusion and then at study follow-up visits at 1, 2, 3, 4 and 6 weeks, and 3 months after the infusion. Blood should come from the central intravenous line, and should not require extra needle sticks.
All participants on this study will be infused with the same number (dose) of cells. If Viralym-B 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 4 additional infusions of the Viralym-B cells at the same initial dose level from 28 days after their initial infusion. Following infusions should be at least 14 days apart. After each Viralym-B cells infusion, subjects will be monitored as described above.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Viralym-B | Experimental | Biological: Viralym-BPartially HLA-matched Viralym-B cells will be thawed and given by intravenous injection. Patients will receive 2 x 10^7 partially HLA-matched Viralym-B/m2 as a single infusion. If a patient has a partial response they are eligible to receive up to 4 additional doses at biweekly intervals. These doses would come from the original infused line if sufficient vials were available but may come from another line if there are insufficient cells in the original line. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells or single or double cord blood within 24 months.
- Persistent or recurrent BK virus infection or disease despite at least 7 days of standard therapy or failure of therapy as described below or if unable to tolerate standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function.
- Clinical status at enrollment to allow tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent).
- Hemoglobin (HgB)>8.0 (may be transfused)
- Received transplant care locally and will remain in the Houston area for at least 6 weeks post Viralym B infusion
Key exclusion criteria (6 listed)
- Patients receiving (Anti-thymocyte globulin) ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of treatment with Viralym-B
- Patients with other uncontrolled/progressing infections defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. 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. 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 of Viralym-B infusion.
- Patients who have received other investigational drugs within 28 days of Viralym-B infusion
- Patients with active acute Graft versus host disease (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 |
|---|---|---|
| Viralym-BFollow-up Assessments: The timing of follow-up visits is based on the date of Viralym-B infusion. If a patient has multiple Viralym-B infusions the schedule resets again at the beginning so follow up relates to the last Viralym-B infusion. Follow up will occur at 7 days, 14 days, 21 days, 28 days, 42 days, 90 days, 180 days, and 365 days post enrollment. | Biological | Viralym-B |
Primary outcome
Assessment of patients with adverse events after Viralym-B infusion
Time frame: 42 days
To determine if administration of banked BKV-specific T cells (Viralym-B) derived from healthy donors are safe in patients with BKV infection after allogeneic stem cell transplant.
2 secondary outcomes
Assessment of BK viral load response to the Viralym-B infusion
Time frame: 1 year
Reconstitution of antiviral immunity after Viralym-B infusion
Time frame: 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2018.
- Background: PubMed 23610374Leen AM, Bollard CM, Mendizabal AM, Shpall EJ, Szabolcs P, Antin JH, Kapoor N, Pai SY, Rowley SD, Kebriaei P, Dey BR, Grilley BJ, Gee AP, Brenner MK, Rooney CM, Heslop HE. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013 Jun 27;121(26):5113-23. doi: 10.1182/blood-2013-02-486324. Epub 2013 Apr 22.
- Background: 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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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.
Swati Naik, MD principal investigator
Texas Childrens Hospital
Bilal Omer, MD principal investigator
The Methodist Hospital Research Institute
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 Viralym-B in people with BK Virus 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 12 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: withdrawn, as of the sponsor's last update on 9 Apr 2018. 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 was withdrawn before enrolling participants, so there are no results.
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?
Assessment of patients with adverse events after Viralym-B infusion (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 NCT02313844, 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 9 Apr 2018.