R-MVST Cells for Treatment of Viral Infections in Children and Young Adults
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age3-26
SponsorMonica Bhatia
About this trial
The primary objective is to determine the safety and feasibility of administering R-MVST cells to patients with refractory viral reactivation and/or symptomatic disease caused by Epstein Barr Virus (EBV), cytomegalovirus (CMV), adenovirus (ADV) or BK virus. R-MVST cells will be generated on-demand from the closest partially human leukocyte antigen (HLA)-matched (minimum haploidentical) healthy donors or from the original allo-transplant donor if available. The investigator will closely monitor the recipients for potential toxicities including graft-versus-host disease (GVHD) post-infusion.
Secondary objectives are to determine the effect of R-MVST infusion on viral load, possible recovery of antiviral immunity post-infusion and for evidence of clinical responses and overall survival. Recipients will be monitored for secondary graft failure at day 28 post R-MVST infusion.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Children and young adults (3 months to <26 years) 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".
Disqualifiers
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 immunosuppressive 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.
Trial design
Design model
Sequential
Treatments tested in this trial
Rapidly generated virus specific T (R-MVST) cells
DrugGroup A dose escalation schedule: * Cohort (-1A): 0.25x10\^6 R-MVST TNC/kg * Cohort (1A): 0.5x10\^6 R-MVST TNC/kg * Cohort (2A): 1x10\^6 R-MVST TNC/kg Groups B \& C dose escalation schedule: * Cohort (-1B) + (-1C): 1x10\^6 R-MVST TNC/kg * Cohort (1B) + (1C): 2x10\^6 R-MVST TNC/kg * Cohort (2B) + (2C): 4x10\^6 R-MVST TNC/kg
Treatment groups
18 Participants
are divided into 3 treatment groupsGroup A: Group A: Allogenic Stem Cell Transplant RecipientsExperimental treatment 1 intervention
Group B: Group B: Solid Organ Transplant RecipientsExperimental treatment 1 intervention
Group C: Group C: Other Immunocompromised PatientsExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of toxicity that leads to safety endpoint
This is to measure the incidence of toxicity post-infusion. Toxicities to consider include: GI toxicity, renal toxicity, hemorrhagic toxicity, cardiovascular toxicity hypotension, cardiac arrhythmia and left ventricular systolic dysfunction), neurological toxicity (somnolence and seizure), coagulation toxicity, vascular toxicity and pulmonary toxicity.
Time frame
Up to 28 days post R-MVST infusion2
Incidence of GVHD post-infusion that leads to safety endpoint
This is to measure the incidence of GVHD post-infusion. The safety endpoint will be defined as de novo acute GVHD grade IV within 28 days of the last dose of R-MVST, or grades 3-5 infusion related adverse events within 28 days of the last cytotoxic T-lymphocyte (CTL) dose, or grades 4-5 non-hematological adverse events within 28 days of the last CTL dose that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.
Time frame
Up to 28 days post R-MVST infusionSecondary outcomes
1
Percentage of subjects with good response in viral load or end-organ disease improvement
This is to measure the effect of R-MVST infusion on viral load and possible recovery of antiviral immunity post-infusion. Subjects with complete response, partial response and stable disease will be tallied. If patient has end-organ involvement, the disease will be monitored for the evidence of clinical response. In case of post-transplant lymphoproliferative disorder (PTLD)/EBV lymphoma, the standard Cheson criteria will be applied for adult patients.
Time frame
Up to 1 year after the initial R-MVST infusion2
Overall survival rate
This is to measure the effect of R-MVST infusion on viral load and possible recovery of antiviral immunity post-infusion. The overall survival rate is defined as the percentage of people in a study or treatment group who are still alive for a certain period of time after they were diagnosed with or started treatment for a disease, such as cancer.
Time frame
Up to 1 year after the initial R-MVST infusion3
Incidence of secondary graft failure
Secondary graft failure is defined as initial neutrophil engraftment followed by subsequent decline in the absolute neutrophil count (ANC) to \< 500/mm3 for three consecutive measurements on different days, unresponsive to growth factor therapy that persists for at least 14 days in the absence of a known cause such as relapse. Secondary graft failure will be assessed at 28 days post R-MVST infusion in allo-HCT recipients and in recipients of solid organ transplantation.
Time frame
Day 28 post R-MVST infusionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Monica Bhatia
Lead sponsor
Columbia University
Sponsor institution
Source ClinicalTrials.gov