Treatment of viral infections using rapidly generated T cells
Phase I Study of Adoptive Immunotherapy of Refractory Viral Infection with Ex Vivo Expanded Rapidly Generated Virus Specific T (R-MVST) Cells
This study is testing a new treatment using specially made T cells to help patients with weakened immune systems who are struggling with serious viral infections like Epstein-Barr or cytomegalovirus.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Columbia University Academic / other |
| Drugs / interventions | Alemtuzumab, nivolumab, pembrolizumab, ipilimumab, methotrexate, prednisone, rituximab |
| Locations | 1 site (New York, New York) |
| Trial ID | NCT05183490 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and feasibility of administering rapidly generated virus specific T cells (R-MVST) to patients suffering from refractory viral reactivation or symptomatic disease caused by Epstein-Barr Virus (EBV), cytomegalovirus (CMV), adenovirus (ADV), or BK virus. The R-MVST cells will be produced on-demand from partially HLA-matched healthy donors or the original allo-transplant donor if available. Participants will be closely monitored for potential toxicities, including graft-versus-host disease (GVHD), and the study will assess the impact of R-MVST infusion on viral load, recovery of antiviral immunity, clinical responses, and overall survival. The trial focuses on patients with weakened immune systems who are at risk of severe complications from these viral infections.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with a history of hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) who exhibit evidence of viral reactivation or infection.
Not a fit: Patients who do not have a history of HCT or SOT and are not experiencing viral reactivation or symptomatic disease from the targeted viruses may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with severe viral infections that are resistant to standard antiviral therapies.
How similar studies have performed: While the approach of using rapidly generated virus specific T cells is innovative, similar studies targeting viral infections in immunocompromised patients have shown promise, suggesting potential for success.
Eligibility criteria
Show full inclusion / exclusion criteria
Recipient Inclusion Criteria: * Men and women ages 18 years or older of all ethnic groups will be eligible for the treatment * Patients with history of HCT or SOT who demonstrate evidence of viral reactivation and/or infection manifesting as end-organ or systemic disease due to one or more of the following viruses: EBV, CMV, ADV or BK virus and suboptimal response to the standard of care therapy. * Recurrent or Multiple Viral Infection. RVI defined as occurrence of more than one episode of reactivation that required intervention or symptomatic disease in recipient of allogeneic HCT that required standard of care treatment. MVI defined as more than one virus reactivating (defined by PCR positivity) or causing symptomatic systemic or end-organ disease. At least one of those viral reactivations required standard of care intervention. No standard of care therapy is defined for ADV and BK. Patients with multiple infections/reactivations will be eligible as long as at least one of those viral infections meet the criterium of "refractory". Recipient Exclusion Criteria: * Patients with other uncontrolled infections, except for CMV, EBV, ADV or BK. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to the day of infusion. For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to R-MVST infusion. 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 receive corticosteroids at ≥ 0.5mg/kg prednisone or equivalent. * Patients who received anti-thymocyte globulin (ATG, Alemtuzumab (Campath), or other T-Cell immunosupressive monoclonal antibodies in the last 28 days. * Patients who received methotrexate, or other antimetabolite-type immunosuppressants that are toxic to proliferating T cells in the last 7 days. * Patients who received extracorporeal photopheresis within the last 28 days. * Patients who received checkpoint inhibitor agents (e.g., nivolumab, pembrolizumab, ipilimumab) within 3 drug half-lives of the most recent dose to the infusion of R-MVST. * Received donor lymphocyte infusion in last 28 days. * Evidence of GVHD ≥ grade 2 * Evidence of biopsy-proven acute rejection in SOT recipients * Active and uncontrolled relapse of malignancy * Patients who are pregnant, or breastfeeding. * Female of childbearing potential, or male with a female partner of childbearing potential, unwilling to use a highly effective method of contraception. * Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients who have received investigational (IND) product within 14 days of infusion of the the R-MVST cells. Donor inclusion and exclusion criteria will be followed as per the most current BMT SOP (Donor selection, Donor evaluation and Donor Deferral).
Where this trial is running
New York, New York
- Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
Study contacts
- Principal investigator: Pawel Muranski, MD — Assistant Professor of Medicine and Pathology and Cell Biology
- Study coordinator: Nurse Navigator
- Email: cancerclinicaltrials@cumc.columbia.edu
- Phone: (212) 342 5162
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.