Donor T Cell Therapy for Adenovirus Infections
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Prednisone, ATG, Campath, others
Disqualifiers: Uncontrolled infections, Active GVHD, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This phase I trial studies the side effects of allogeneic adenovirus-specific cytotoxic T lymphocytes (donor T cell therapy) and to see how well they work in treating patients with a weakened immune system (immunocompromised) and adenovirus-related disease. Allogeneic adenovirus-specific cytotoxic T lymphocytes are made from donated blood cells grown in the laboratory and are designed to kill viruses that can cause infections in immunocompromised patients with adenovirus-related disease.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain high doses of prednisone or have recently received specific treatments like anti-thymocyte globulin or donor lymphocyte infusion.
What data supports the effectiveness of the treatment Donor T Cell Therapy for adenovirus infections?
Research shows that using virus-specific T cells (VSTs) to treat adenovirus infections in patients who have had stem cell transplants is highly effective, with 81% of patients showing improvement and 58% achieving complete recovery. This approach is particularly beneficial for those with weakened immune systems, as traditional antiviral drugs often have limited success and can cause significant side effects.12345
Is Donor T Cell Therapy for Adenovirus Infections safe for humans?
Research indicates that Donor T Cell Therapy, also known as Virus-Specific T Cells (VSTs), is generally safe for treating adenovirus infections in humans, especially in those with weakened immune systems. Studies have shown that this therapy can effectively manage viral infections without significant acute toxicity or increased risk of graft-versus-host disease (a condition where donor cells attack the recipient's body).15678
How is Donor T Cell Therapy different from other treatments for adenovirus infections?
Donor T Cell Therapy is unique because it uses virus-specific T cells from a donor to help the patient's immune system fight adenovirus infections, especially in those with weakened immune systems after stem cell transplants. Unlike traditional antiviral drugs, which can have limited effectiveness and significant side effects, this therapy directly boosts the body's ability to target and eliminate the virus.12357
Research Team
David Marin
Principal Investigator
M.D. Anderson Cancer Center
Eligibility Criteria
This trial is for immunocompromised patients with blood cancers and asymptomatic adenovirus viremia, or those showing probable or definitive signs of the disease. Participants must consent, not be pregnant, agree to use contraception if applicable, and cannot have certain uncontrolled infections or recent treatments that suppress the immune system.Inclusion Criteria
I am not pregnant and willing to use birth control during the study.
I have a virus in my blood but feel fine, confirmed by tests.
I have been diagnosed with an adenoviral disease.
See 2 more
Exclusion Criteria
I am not currently taking high doses of prednisone, nor have I recently received specific immune treatments.
I have no worsening infections and am on treatment if I have any.
I have a severe reaction from a transplant.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2 weeks
Treatment
Participants receive allogeneic adenovirus-specific cytotoxic T lymphocytes intravenously over 30 minutes. Additional infusions may be given at the discretion of the investigator.
2 weeks
1 visit (in-person)
Follow-up
Participants are monitored for safety, efficacy, and persistence of the administered cells after treatment
12 months
Regular visits as per study protocol
Treatment Details
Interventions
- Donor T Cell Therapy (T-cell Therapy)
Trial OverviewThe study tests donor T cell therapy using allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs) in patients with weakened immune systems due to blood cancers. These CTLs are grown from donated cells aimed at fighting off adenovirus infections.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (allogeneic adenovirus-specific CTLs)Experimental Treatment1 Intervention
Within two weeks of enrollment, patients receive allogeneic adenovirus-specific CTLs IV over 30 minutes. Patients may receive additional allogeneic adenovirus-specific CTL infusions at the discretion of the investigator in the absence of disease progression or unacceptable toxicity.
Donor T Cell Therapy is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Allogeneic Adenovirus-Specific Cytotoxic T Lymphocytes for:
- Adenovirus-related disease in immunocompromised patients
🇪🇺 Approved in European Union as Donor-Derived Adenovirus-Specific CTLs for:
- Refractory adenovirus infections post allogeneic hematopoietic stem cell transplantation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer Center
Lead Sponsor
Trials
3107
Patients Recruited
1,813,000+
National Cancer Institute (NCI)
Collaborator
Trials
14080
Patients Recruited
41,180,000+
References
Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. [2022]Infection with adenoviruses is a common and significant complication in pediatric patients after allogeneic hematopoietic stem cell transplantation. Treatment options with traditional antivirals are limited by poor efficacy and significant toxicities. T-cell reconstitution is critical for the management of adenoviral infections, but it generally takes place months after transplantation. Ex vivo-generated virus-specific T cells (VSTs) are an alternative approach for viral control and can be rapidly generated from either a stem cell donor or a healthy third-party donor. In the context of a single-center phase 1/2 clinical trial, we treated 30 patients with a total of 43 infusions of VSTs for adenoviremia and/or adenoviral disease. Seven patients received donor-derived VSTs, 21 patients received third-party VSTs, and 2 received VSTs from both donor sources. Clinical responses were observed in 81% of patients, with a complete response in 58%. Epitope prediction and potential epitope identification for common HLA molecules helped elucidate HLA restriction in a subset of patients receiving third-party products. Intracellular interferon-γ expression in T cells in response to single peptides and response to cell lines stably transfected with a single HLA molecule demonstrated HLA-restricted CD4+ T-cell response, and these results correlated with clinical outcomes. Taken together, these data suggest that VSTs are a highly safe and effective therapy for the management of adenoviral infection in immunocompromised hosts. The trials were registered at www.clinicaltrials.gov as #NCT02048332 and #NCT02532452.
Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. [2019]In patients with lymphopenia following allogeneic stem cell transplantation adenovirus (ADV) infection is associated with high morbidity and mortality despite aggressive antiviral drug therapy. Virus-specific T cells seem to be essential for virus elimination. The aim of this study was to isolate and expand donor-derived human ADV-specific T lymphocytes for adoptive transfer of sufficient cell numbers to restore protective immunity after allogeneic stem cell transplantation.
T-cell immunotherapy for adenoviral infections of stem-cell transplant recipients. [2007]Human adenoviruses are ubiquitous lytic DNA viruses that can be divided into 51 different serotypes, grouped from A to F on the basis of genome size, composition, homology, and organization. Adenovirus infections, although frequent, are rarely fatal in immunocompetent individuals, due to potent innate and adaptive immune responses. By contrast, adenoviruses are a significant cause of morbidity and mortality in immunosuppressed individuals, for whom there are limited treatment options. Since antiviral drugs have variable efficacy in the treatment of severe adenovirus disease, iatrogenic reconstitution with in vitro expanded virus-specific cytotoxic T lymphocytes (CTLs) is an attractive option for prophylaxis and treatment, particularly because the endogenous recovery of adenovirus-specific T cells has proved important in controlling infection in vivo. Thus, we have characterized human T-cell responses to adenovirus in vitro and explored the potential of adoptive T-cell immunotherapy as a prophylactic or therapeutic strategy for adenovirus infections posttransplant.
Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. [2008]Human adenovirus (ADV) infection is an important complication post allogeneic stem cell transplantation (SCT), especially in children, with significant morbidity and mortality despite new antiviral treatment strategies. Although the control of infection seems to require T cells, characterization of ADV-specific T cells post-SCT has not been reported to date. Therefore, we prospectively studied the occurrence of ADV-specific T cells in children with (n = 21) and without (n = 25) ADV-infection postallogeneic SCT and in healthy donors (n = 53). ADV-associated mortality occurred in seven of 21 children. After stimulation ex vivo with ADV-lysate, interferon-gamma-secreting T cells were analysed by flow cytometry. All the patients with ADV-associated mortality had no specific T cells, although reconstitution of absolute lymphocyte counts exceeded 0.3 x 10(9)/l within 30 d post-transplant. Patients who cleared ADV infection had significantly higher frequencies (mean +/- standard deviation, 0.56 +/- 0.5%) of ADV-specific T cells until day 200 post-SCT, than patients without ADV-infection (0.12 +/- 0.1%). These data suggest that ADV-specific T-cell reconstitution is protective against life-threatening ADV-infections postallogeneic SCT.
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.
Adoptive T-cell immunotherapy from third-party donors: characterization of donors and set up of a T-cell donor registry. [2022]Infection with and reactivation of human cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) are frequent and severe complications in immunocompromised recipients after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT). These serious adverse events are associated with significant morbidity and mortality. Donor lymphocyte infusions (DLIs) are often used to treat both viral infections and leukemia relapses after transplantation but are associated with potentially life-threatening graft-versus-host disease (GvHD). Adoptive immunotherapy with virus-specific cytotoxic effector T cells (CTLs) derived from seropositive donors can rapidly reconstitute antiviral immunity after HSCT and organ transplantation. Therefore, it can effectively prevent the clinical manifestation of these viruses with no significant acute toxicity or increased risk of GvHD. In conditions, where patients receiving an allogeneic cord blood (CB) transplant or a transplant from a virus-seronegative donor and since donor blood is generally not available for solid organ recipients, allogeneic third party T-cell donors would offer an alternative option. Recent studies showed that during granulocyte colony-stimulating factor (G-CSF) mobilization, the functional activity of antiviral memory T cells is impaired for a long period. This finding suggests that even stem cell donors may not be the best source of T cells. Under these circumstances, partially human leukocyte antigen (HLA)-matched virus-specific CTLs from healthy seropositive individuals may be a promising option. Therefore, frequency assessments of virus-specific memory T cells in HLA-typed healthy donors as well as in HSCT/SOT donors using a high throughput T-cell assay were performed over a period of 4 years at Hannover Medical School. This chapter will address the relevance and potential of a third-party T-cell donor registry and will discuss its clinical implication for adoptive T-cell immunotherapy.
Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial. [2018]Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB).
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.