Clinical trial NCT03425526: Donor T Cell Therapy in Treating Immunocompromised Patients With Adenovirus-Related Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hematopoietic and Lymphoid Cell Neoplasm
Immunocompromised
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-02-07
Enrollment: 16
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0
timeFrame: Up to 1 year
measure: Assessment of response to allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From the start of study treatment up to 1 year
measure: Relapse-free survival (RFS)
timeFrame: From the start of study treatment up to 1 year
measure: Cumulative incidence of adenovirus reactivation after therapy
timeFrame: Up to 1 year
measure: Cumulative incidence of graft versus host disease (GVHD)
timeFrame: Up to 1 year
measure: Reconstitution of anti-adenovirus immunity
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: David Marin
role: PRINCIPAL_INVESTIGATOR
References: