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RecruitingInterventionalPhase 1

Administration of Off-the-Shelf, Expanded, Most Closely HLA Matched, Third Party Adenovirus Specific T Cells for Therapy of Adenovirus Related Disease in Immunocompromised Patients

NCT ID: NCT03425526Sponsor: M.D. Anderson Cancer CenterLast updated: 2026-02-19

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. To assess the feasibility and safety of administering most closely human leukocyte antigen (HLA)-matched adenovirus specific T cell lines generated by ex vivo expansion as therapy of asymptomatic adenovirus viremia or adenovirus-related disease in immunocompromised hosts. SECONDARY OBJECTIVES: I. To obtain preliminary data about the efficacy of administering most closely HLA-matched adenovirus specific T cell lines generated by ex vivo expansion as therapy of adenovirus viremia or adenovirus-related disease. II. To assess the persistence of the administered cells in the patients. OUTLINE: Within two weeks of enrollment, patients receive allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs) intravenously (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. After completion of study treatment, patients are followed up for 12 months.

Arms & interventions

  • BiologicalAllogeneic Adenovirus-specific Cytotoxic T Lymphocytes

    Given IV

Outcome measures

Primary

  • Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0

    Safety and tolerability will be assessed by laboratory assessments, adverse events, and serious adverse events. Adverse events will be graded by the CTCAE version 4.0. Categorical measures will be summarized using frequencies and percentages while continuous variables will be summarized using means, standard deviations, medians, minimums, and maximums.

    Time frame: Up to 1 year

  • Assessment of response to allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs)

    The proportion of patients experiencing response will be computed with associated 95% confidence interval (CI). The 95% exact CI for the feasibility criterion of 50% will extend from 25% to 75% for 16 patients.

    Time frame: Up to 1 year

Secondary

  • Overall survival (OS)

    Time frame: From the start of study treatment up to 1 year

  • Relapse-free survival (RFS)

    Time frame: From the start of study treatment up to 1 year

  • Cumulative incidence of adenovirus reactivation after therapy

    Time frame: Up to 1 year

  • Cumulative incidence of graft versus host disease (GVHD)

    Time frame: Up to 1 year

  • Reconstitution of anti-adenovirus immunity

    Time frame: Up to 1 year

Eligibility criteria

Sex: AllAge: All agesHealthy volunteers: No
Inclusion Criteria: * Immunocompromised patients. * English and non-English speaking patients. * Written informed consent and/or signed assent from patient, parent or guardian. * Negative pregnancy test in female patients of childbearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study. * Patients age 1 year or older with asymptomatic adenovirus viremia defined as no symptoms of adenovirus disease and EITHER two positive and quantifiable qPCR tests taken one week apart or one single measurement with \>/= 1000 copies. * Patients age 1 year or older with criteria of probable or definitive adenoviral diseases as defined in Appendix A. * Willingness to comply with the study protocol requirements. Exclusion Criteria: * Patients receiving prednisone \> 0.1 mg/kg/day or equivalent at time of enrollment, or who have received anti-thymocyte globulin (ATG) within 14 days or have received donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment. * Patients with other uncontrolled infections: For bacterial infections, patients must be receiving therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. 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. * Active acute graft versus host disease (GVHD) grade \>= 2.

Study locations (1)

M D Anderson Cancer Center

Houston, Texas, 77030

Recruiting
David Marin · Contact
David Marin · Principal Investigator