Adenovirus Infection Clinical Trial
Official title:
A Phase I Study Using Most Closely HLA-matched Adenovirus-specific T Lymphocytes for the Treatment of Adenovirus Infections Post-allogeneic Stem Cell Transplant(VIRALYM-A)
Verified date | July 2018 |
Source | ViraCyte |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Adenovirus (AdV) is a virus that just causes symptoms of a common cold normally, but which
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.
Investigators want to see if they can use a kind of white blood cell called T cells to treat
adenovirus 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 AdV-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 AdV.
In this study, investigators want to find out if the banked AdV-specific T cells derived from
healthy donors are safe and can help to treat adenoviral infection.
The AdV-specific T cells (Viralym-A) are an investigational product not approved by the Food
and Drug Administration (FDA).
Funding source - FDA OOPD
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | December 2019 |
Est. primary completion date | December 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility |
Inclusion Criteria: 1. 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. 2. Persistent or recurrent adenovirus 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. Adenovirus infection: defined as the presence of adenoviral positivity as detected by polymerase chain reaction (PCR) or culture from ONE site, such as stool or blood or urine or nasopharynx. ii. Adenovirus disease: defined as the presence of adenoviral positivity as detected by PCR, Direct fluorescent assay (DFA) or culture from two or more sites such as stool or blood or urine or nasopharynx. 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. 3. Patients with multiple viral infections including AdV are eligible if their AdV infection is persistent despite standard therapy as defined above. Patients with multiple infections with one or more reactivation and one or more controlled infection are eligible to enroll. 4. Clinical status at enrollment to allow tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent). 5. Received transplant care locally and will remain in the Houston area for at least 6 weeks post Viralym-A infusion. 6. Hemoglobin (Hgb) > 8.0 (may be transfused). 7. Available Viralym-A T cell line. 8. Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen). 9. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. Exclusion Criteria: 1. Patients receiving Anti-thymocyte globulin (ATG), Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of treatment with Viralym-A. 2. 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. 3. Patients who have received donor lymphocyte infusion (DLI) within 28 days of Viralym-A infusion. 4. Requirement for FiO2 > 0.5 to maintain arterial oxygen saturation > 90% 5. Endotracheal intubation and mechanical ventilation at any FiO2 6. Hemodynamic instability requiring continuous infusions of inotropes or vasopressors 7. Patients who have received other investigational drugs within 28 days of Viralym-A infusion. 8. Patients with active acute graft versus host disease (GVHD) grades II-IV. 9. Active and uncontrolled relapse of malignancy. |
Country | Name | City | State |
---|---|---|---|
United States | Texas Childrens Hospital | Houston | Texas |
United States | The Methodist Hospital system | Houston | Texas |
Lead Sponsor | Collaborator |
---|---|
ViraCyte | Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital System |
United States,
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. — View 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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Assessment of patients with adverse events after Viralym-A infusion | To determine if administration of banked AdV-specific T cells (Viralym-A) derived from healthy donors are safe in patients with AdV infection after allogeneic stem cell transplant. | 42 days | |
Secondary | Assessment of adenoviral load response to the Viralym-A 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. | 1 year | |
Secondary | Reconstitution of antiviral immunity after Viralym-A 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. | 3 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04722029 -
Pilot Study of Haploidentical Donor Adenovirus Specific T-lymphocytes to Treat Refractory Adenovirus Infections
|
Phase 1/Phase 2 | |
Completed |
NCT00711035 -
Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)
|
Phase 1/Phase 2 | |
Completed |
NCT00880789 -
Safety, Toxicity and MTD of One Intravenous IV Injection of Donor CTLs Specific for CMV and Adenovirus
|
Phase 1 | |
Terminated |
NCT05305040 -
Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant
|
Phase 2/Phase 3 | |
Completed |
NCT02087306 -
Study to Assess the Safety and Efficacy of Brincidofovir in Treatment of Early Versus Late Adenovirus Infection
|
Phase 3 | |
Active, not recruiting |
NCT03475212 -
Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation
|
Phase 1/Phase 2 | |
Completed |
NCT00590083 -
Administration of Virus-Specific Cytotoxic T-Lymphocytes
|
Phase 1 | |
Recruiting |
NCT03159364 -
Antigen-specific Cytotoxic T Cells in the Treatment of Opportunistic Infections
|
Phase 1/Phase 2 | |
Recruiting |
NCT05101213 -
Study Assessing the Feasibility, Safety and Efficacy of Genetically Engineered Glucocorticoid Receptor Knock Out Virus Specific CTL Lines for Viral Infections in Immunosuppressed Cancer Patients
|
Phase 1 | |
Completed |
NCT01070797 -
Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes (VIRAGE)
|
Phase 1 | |
Completed |
NCT04693637 -
Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant
|
Phase 2/Phase 3 | |
Recruiting |
NCT02007356 -
A Study to Assess Safety and Feasibility of Direct Infusions of Donor-derived Virus-specific T-cells in Recipients of Hematopoietic Stem Cell Transplantation With Post-transplant Viral Infections Using the Cytokine Capture System®
|
Phase 2 | |
Withdrawn |
NCT02702427 -
Virus-specific ImmunoTherapy Following Allogeneic Stem Cell Transplantation
|
Phase 1/Phase 2 | |
Completed |
NCT02851576 -
Clinical Grade Adenovirus Specific T Cells for Immunotherapy After Allogeneic Stem Cell Transplantation (CTL-ADV)
|
Phase 1/Phase 2 | |
Terminated |
NCT05179057 -
Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation
|
Phase 3 |