Donor T Cell Therapy in Treating Immunocompromised Patients With Adenovirus-Related Disease

M.D. Anderson Cancer Center

Status and phase: Enrolling; Phase 1

Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Immunocompromised

Treatments: Biological: Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03425526

2017-0350 (Other Identifier)

NCI-2018-00929 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

Treatment (allogeneic adenovirus-specific CTLs)

Experimental group

Description:

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.

Treatment:

Biological: Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes