Back to resultsMost Closely Human Leukocyte Antigen (HLA)-Matched BK Virus-specific T Lymphocytes (Viralym-B)
Primary Purpose
BK Virus Infection
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Viralym-B
Sponsored by
About this trial
This is an interventional treatment trial for BK Virus Infection focused on measuring BK virus, Virus specific T cells, Viral infections
Eligibility Criteria
Inclusion Criteria:
- 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.
i. 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.
ii. 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.
iii. 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).
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Texas Childrens Hospital
- The Methodist Hospital system
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Viralym-B
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02313844
Brief Title
Most Closely Human Leukocyte Antigen (HLA)-Matched BK Virus-specific T Lymphocytes (Viralym-B)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Not developing product
Study Start Date
March 1, 2018 (Anticipated)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AlloVir
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
BK Virus Infection
Keywords
BK virus, Virus specific T cells, Viral infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Viralym-B
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Viralym-B
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assessment of patients with adverse events after Viralym-B infusion
Description
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.
Time Frame
42 days
Secondary Outcome Measure Information:
Title
Assessment of BK viral load response to the Viralym-B infusion
Description
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.
Time Frame
1 year
Title
Reconstitution of antiviral immunity after Viralym-B infusion
Description
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.
Time Frame
3 months
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
i. 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.
ii. 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.
iii. 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).
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Swati Naik, MD
Organizational Affiliation
Texas Childrens Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bilal Omer, MD
Organizational Affiliation
The Methodist Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas Childrens Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Methodist Hospital system
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23610374
Citation
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.
Results Reference
background
PubMed Identifier
24964991
Citation
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.
Results Reference
background
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Most Closely Human Leukocyte Antigen (HLA)-Matched BK Virus-specific T Lymphocytes (Viralym-B)
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