Antigen Specific Adoptive T Cell Therapy for Adenovirus Infection After Hematopoietic Stem Cell Transplantation

NCT03378102 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: CASE4Z17
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if it is possible to treat an infection with a cell-based immunotherapy (therapy that uses the patient's own immune system to treat the infection). This treatment is called adoptive T cell therapy. Another purpose is to learn about the side effects and toxicities of adoptive T cell therapy. Adoptive T cell therapy is an investigational (experimental) therapy that works by using the blood of a donor that has immunity against the virus. The donor cells are collected and then the cells, called T cells, that are capable of defending against the virus are selected out. These selected T cells are then infused back into the patient, to try to give the immune system the ability to fight the infection. Adoptive T cell therapy is experimental because it is not approved by the Food and Drug Administration (FDA).

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation

Keywords

T Cell Therapy; Opportunistic Infection

Outcome Measures

Primary Outcomes (1)

• Number of patients with severe adverse events

  This is a measure of feasibility: Severe adverse events are related to the infusion of virus-specific, antigen selected T cells, Grade ≥ 3 acute graft versus host disease,• Death within 30 days of the infusion of the virus-specific, antigen selected T cells that is considered by the investigators to be probably or possibly related to the T cell infusion

  Up to 100 days after infusion

Secondary Outcomes (4)

• Number of patients with viral response

  Up to 30 days after infusion

• Number of patients with clinical response

  Up to 30 days after infusion

• Time from enrollment to T cell product infusion

  Up to 24 hours

• Time from peripheral mononuclear cell collection to T cell product infusion

  Up to 15 hours

Study Arms (1)

Interferon (IFN)-gamma-secreting HAdV antigen specific T cells

EXPERIMENTAL

Virus-specific, antigen selected cells will be obtained using the CliniMACS® Prodigy System. The donor will be screened for their ability to produce an IFN-gamma- secretion response to HAdV by testing the donor's mononuclear cells with the Miltenyi Rapid Cytokine Inspector kit. Donors with appropriate IFN-gamma secretion response will undergo a steady state leukapheresis. The investigational product (IP) will be generated using the CCS-IFN enrichment program with an approximate duration time of 15 hours. IP will be suspended in 0.9 normal saline + 2.5% albumin and distributed for infusion and infused within 4 hours as a bolus on day 0. Subjects will receive virus-specific, antigen selected T cells within a targeted range of 1 x 10\^3- 2 x 10\^5 per kg of recipient weight.

Biological: IFN-gamma-secreting HAdV antigen specific T cells

Interventions

IFN-gamma-secreting HAdV antigen specific T cells BIOLOGICAL

Antigen selected cells will be obtained using the CliniMACS(R) Prodigy System from a compatible donor. Isolated cells will be infused into the donor to treat human adenoviral infection after transplant

Also known as: Antigen-selected, adenovirus-specific T Cells

Interferon (IFN)-gamma-secreting HAdV antigen specific T cells

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have received allogeneic HSCT and be greater than 30 days post-HSCT at the time of registration.
• Patients must have evidence of documented HAdV infection/reactivation. Patients may be:
• Symptomatic with any detectable viral load OR
• Asymptomatic with viral load that is:
• \>1000 copies/ml in peripheral blood OR qualitative detection in stool, urine and/or other specimens
• Patients must have poor response and/or contraindication to therapy:
• Absence of an improvement of viral load (decrease by at least 1 log, i.e. 10-fold) after ≥ 14 days of antiviral therapy with ganciclovir, valganciclovir and/or foscarnet. OR
• New, persistent and/or worsening HAdV-related symptoms, signs and/or markers of end organ compromise while on antiviral therapy with ganciclovir, valganciclovir or foscarnet. OR
• Have contraindications or experience adverse effects of antiviral therapy with ganciclovir, valganciclovir, cidofovir or foscarnet.
• Performance Score: Eastern Cooperative Oncology Group (ECOG) Performance Score ≤ 3. Karnofsky (≥ 16 years) or Lansky (\<16 years) performance score ≥ 50
• The effects of virus-specific, antigen-selected T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 4 weeks prior to study entry, for the duration of study participation and for 3 months after completing treatment.
• Subjects who are 14 years and older must have the ability to understand and the willingness to sign a written informed consent document, or assent document.

You may not qualify if:

• Pregnant or breastfeeding women are excluded from this study. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with the agents described above, breastfeeding should be discontinued if the mother participates in this trial.
• Patients with opportunistic viral infections other than HAdV.
• Patients with active, grade II-IV, acute graft versus host disease (GVHD), chronic GVHD or any condition requiring high doses of glucocorticosteroid (\>0.5 mg/kg/day prednisone or its equivalent) as treatment.
• Treatment with antithymocyte globulin within 28 days of planned infusion of virus - specific, antigen selected T cells.
• Treatment with virus - specific T cells within 6 weeks (42 days) of planned infusion.

Sponsors & Collaborators

• Mari Dallas: lead

Study Sites (1)

University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Opportunistic Infections

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Mari H Dallas, MD

  University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mari H Dallas, MD

CONTACT

216-844-0139; mhd27@case.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: December 19, 2017
• Study Start: January 4, 2019
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-06

Locations

US (1)