VST Infusion for Post-Transplant Viral Infections
(VSTs Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byMichael Grimley, MD
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Children's Hospital Medical Center, Cincinnati
Must not be taking: ATG, Alemtuzumab
Disqualifiers: Acute GVHD, Uncontrolled infection, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?In this research study, the investigators want to learn more about the use of donor-derived viral specific T-cells (VSTs) to treat viral infections that occur after allogeneic stem cell transplant. A viral specific T cell is a T lymphocyte (a type of white blood cell) that kills cells that are infected (particularly with viruses). Allogeneic means the stem cells come from another person. These VSTs are cells specially designed to fight the virus infections that can happen after a bone marrow transplant.
The investigators are asking people who have undergone or will undergo an allogeneic stem cell transplant to enroll in this research study, because viral infections are a common problem after allogeneic stem cell transplant and can cause significant complications including death.
Stem cell transplant reduces a person's ability to fight infections. There is an increased risk of getting new viral infections or reactivation of viral infections that the patient has had in the past, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), BK virus (BKV), and JC virus. There are anti-viral medicines available to treat these infections, though not all patients will respond to the standard treatments. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study the investigators are trying to find an easier way to treat these infections.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that your clinical status must allow tapering of steroids to a certain level, which might mean adjustments to steroid use.
What data supports the effectiveness of the VST Infusion treatment for post-transplant viral infections?
Research shows that using virus-specific T cells (VSTs) from donors can effectively restore immunity and control viral infections in 70% to 90% of patients after a stem cell transplant. Additionally, a study found that using banked third-party VSTs led to a 74% response rate in patients with severe viral infections, with significant decreases in viral DNA and improvement in symptoms.
12345Is VST infusion safe for humans?
VST infusion appears to be generally safe for humans, with studies showing no serious infusion-related adverse events and only a few cases of mild complications like graft-versus-host disease. The treatment has been well tolerated in patients, with good viral control and clinical outcomes.
23467How is the VST Infusion treatment different from other treatments for post-transplant viral infections?
VST Infusion is unique because it uses virus-specific T cells (VSTs) from donors to restore virus-specific immunity in patients after a transplant, especially when conventional treatments fail. This approach can use banked third-party VSTs, making it a rapid and feasible option for treating severe viral infections without needing to generate a separate line for each patient.
12345Eligibility Criteria
This trial is for people who've had or will have a stem cell transplant from another person and are struggling with viral infections post-transplant. They must have stable white blood cell counts, be able to reduce steroid use, and be at least 21 days past their stem cell infusion. It's not for those recently treated with certain immune suppressants, experiencing severe graft-versus-host disease, uncontrolled bacterial/fungal infections, or cancer relapse.Inclusion Criteria
Recipient must have achieved engraftment with ANC ≥ 500
It has been at least 21 days since my stem cell infusion.
I can reduce my steroid use to a low dose.
Exclusion Criteria
My cancer has returned and is not under control.
I received ATG or alemtuzumab treatment within the last 2 weeks.
I do not have any untreated bacterial or fungal infections.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive donor-derived viral specific T-cells (VSTs) to treat viral infections post-transplant. Up to 5 infusions may be given, with 21 days between each treatment, or 14 days if no viral response is observed.
Up to 15 weeks
Up to 5 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after VST infusion, with physical exams and blood tests weekly until 30 days after the last infusion, and monthly monitoring for 1 year if possible.
12 months
Weekly visits for 1 month, then monthly visits for 1 year
Participant Groups
The study tests the effectiveness of infusing donor-derived T-cells that specifically target viruses in patients after allogeneic stem cell transplants. These special cells aim to combat common but potentially deadly viral infections that can occur when someone's immune system is weakened by a transplant.
1Treatment groups
Experimental Treatment
Group I: Viral Specific VST InfusionExperimental Treatment1 Intervention
Viral reactivation or infection. VST Reinfusion required.
Viral specific VST Infusion is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Viral Specific T-cells for:
- Cytomegalovirus (CMV) infections
- Epstein-Barr virus (EBV) infections
- Adenovirus (ADV) infections
- BK virus (BKV) infections
- JC virus infections
🇪🇺 Approved in European Union as Viral Specific T-cells for:
- Cytomegalovirus (CMV) infections
- Epstein-Barr virus (EBV) infections
- Adenovirus (ADV) infections
- BK virus (BKV) infections
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Akron Children's HospitalAkron, OH
Cincinnati Children's Hospital Medical CenterCincinnati, OH
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
Hoxworth Blood CenterCollaborator
References
High-intensity interval training in allogeneic adoptive T-cell immunotherapy - a big HIT? [2021]Adoptive transfer of virus-specific T cells (VSTs) represents a prophylactic and curative approach for opportunistic viral infections and reactivations after transplantation. However, inadequate frequencies of circulating memory VSTs in the T-cell donor's peripheral blood often result in insufficient enrichment efficiency and purity of the final T-cell product, limiting the effectiveness of this approach.
T cells for viral infections after allogeneic hematopoietic stem cell transplant. [2021]Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches.
Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. [2022]Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n = 50), 73.9% (95% CI, 51.2% -96.6%) for cytomegalovirus (n = 23), 77.8% for adenovirus (n = 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n = 9). Only 4 responders had a recurrence or progression. There were no immediate infusion-related adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035.
Identification of the best-suited donor for generating virus-specific T cells. [2020]Administration of virus-specific T cells (VSTs) is a viable antiviral treatment strategy after allogeneic HSCT, even if conventional therapies fail. Third-party donors are often chosen for the generation of the VST product. The eligibility of the donor has to be tested in a rigorous donor screening procedure, since the isolation technology only targets pre-existing VSTs.
A cost-effective strategy for selection of third-party donors for a virus-specific T-cell bank for an Asian patient population. [2023]Third party virus-specific T cells (VST) has shown efficacy for opportunistic virus infection which do not have effective treatment or are drug-refractory. We describe our preparatory work in setting up a third-party VST bank for a multi-ethnic Asian population.
Third-party CMV- and EBV-specific T-cells for first viral reactivation after allogeneic stem cell transplant. [2022]Virus-specific T-cells (VSTs) from third-party donors mediate short- and long-term antiviral effects in allogeneic hematopoietic stem cell transplant (HSCT) recipients with relapsed or refractory viral infections. We investigated early administration of third-party VSTs, together with antiviral therapy in patients requiring treatment for first cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection. Thirty HSCT patients were treated with 1 to 4 VST infusions (2 × 107 cells/m2; CMV n=27, EBV n=3) at a median of 4 days after initiation of antiviral treatment. The overall viral response rate was 100%, with a complete response (CR) rate of 94%. Of the 28 patients who achieved a CR, 23 remained virus PCR negative (n=9) or below quantitation limit (n=14) for the duration of follow-up. Four patients had brief episodes of quantifiable reactivation not requiring additional therapy, and one required a second infusion after initial CR, remaining PCR negative thereafter. All 3 patients treated for EBV post-transplant lymphoproliferative disorder achieved sustained CR. Rates of aGVHD and cGVHD after infusion were 13% and 23%, respectively. There were no serious infusion-related adverse events. VST infusion was associated with rapid recovery of CD8+CD45RA-CD62L- and a slower recovery of CD4+CD45RA-CD62L- effector memory T-cells; CMV-specific T-cells comprised up to 13% of CD8+ cells. At 1 year post-transplant, non-relapse mortality was 10%, cumulative incidence of relapse was 7%, overall survival was 88% and 25 of 27 patients had ECOG status of 0 or 1. Early administration of third-party VSTs in conjunction with antiviral treatment appears safe and leads to excellent viral control and clinical outcomes. Registered on Australian New Zealand Clinical Trials Registry as #ACTRN12618000343202.
Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. [2019]Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8+ terminal effector cells. PD-1 expression was elevated on CD8+ lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8+ effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.