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

Phase

Condition

Allo-hematopoietic Stem Cell Transplant

Allogeneic Hematopoietic Stem Cell Transplant

Treatment

IFN-gamma-secreting HAdV antigen specific T cells

Clinical Study ID

NCT03378102

CASE4Z17

Ages > 3
All Genders

Study 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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

Patients must have received allogeneic HSCT and be greater than 30 days post-HSCT atthe time of registration.
Patients must have evidence of documented HAdV infection/reactivation. Patients maybe:
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, valganciclovirand/or foscarnet. OR
New, persistent and/or worsening HAdV-related symptoms, signs and/or markers ofend organ compromise while on antiviral therapy with ganciclovir,valganciclovir or foscarnet. OR
Have contraindications or experience adverse effects of antiviral therapy withganciclovir, 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 humanfetus are unknown. For this reason, women of child-bearing potential and men mustagree to use adequate contraception (double barrier method of birth control orabstinence) 4 weeks prior to study entry, for the duration of study participationand for 3 months after completing treatment.
Subjects who are 14 years and older must have the ability to understand and thewillingness to sign a written informed consent document, or assent document.

Exclusion

Exclusion Criteria:

Pregnant or breastfeeding women are excluded from this study. Because there is anunknown, but potential risk for adverse events in nursing infants secondary totreatment of the mother with the agents described above, breastfeeding should bediscontinued 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), chronicGVHD or any condition requiring high doses of glucocorticosteroid (>0.5 mg/kg/dayprednisone 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 plannedinfusion.

Study Design

IFN-gamma-secreting HAdV antigen specific T cells

January 04, 2019

December 31, 2028

Study Description

Brief Background/Rationale: This study seeks to determine the feasibility of using antigen specific T cells isolated with the CliniMACS® Cytokine Capture System (CCS) for the treatment of adenovirus infections occurring after allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Primary Objective: To determine the feasibility of the treatment of opportunistic adenovirus infection after HSCT with adenovirus-specific, antigen-selected T cells, using the CliniMACS® Prodigy System.

Exploratory Objective(s)

To describe the safety profile of the infusion of virus - specific, antigen selected T cells.
To describe the toxicities related to infusion of virus - specific, antigen selected T cells.
To describe the rate of eradication of opportunistic adenovirus infection after treatment with virus-specific, antigen-selected T cells using the CliniMACS® Prodigy System.

Study Design:

This feasibility study will include a single treatment cohort including subjects who have failed to respond, are intolerant or have contraindications to antiviral agents used for treatment of Human Adenovirus (HAdV) (ganciclovir, valganciclovir, foscarnet and cidofovir).

Patients will be enrolled in a staggered pattern to ensure safety.

Patient 1 will be enrolled and observed for 30 days after infusion of virus specific T cells before enrollment of a subsequent patient.
Patient 2 will be enrolled ≥ 30 days after treatment of patient 1 and will be observed for 30 days before enrollment of a subsequent patient.
Subsequent patients will be enrolled in 6 cohorts of 3 subjects each. A safety period between cohorts of 30 days (between treatment of the last subject of one cohort and the first subject of the subsequent cohort).

Study Design: Staggered enrollment of patients with an observation period of 30 days after infusion. Safety monitoring points planned after patient No. 5 and No. 11

Connect with a study center

University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio 44106
United States
Active - Recruiting

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