Overview
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).
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
Eligibility
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.