Clinical trial NCT02982902: T Cell Therapy of Opportunistic Cytomegalovirus Infection
Official title: Antigen Specific Adoptive T Cell Therapy for Opportunistic Cytomegalovirus Infection Occurring After Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Cytomegalovirus Infections
Hematopoietic Stem Cell Transplant
Opportunistic Infections
Keywords: Immunotherapy
T-Cell Therapy
Lymphoproliferative Disorder
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2016-12-06
Enrollment: 20
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to determine if a specific type of cell-based immunotherapy, using T-cells from a donor that are specific against cytomegalovirus (CMV) is feasible to treat infections by CMV.

Adoptive T-cell therapy is an investigational (experimental) therapy that works by using the blood of a donor and selecting the T-cells that can respond against a specific infectious entity. These selected T-cells are then infused to 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).

Detailed description: The primary objective of this study is to determine the feasibility of the treatment of opportunistic cytomegalovirus (CMV) infections after hematopoietic stem cell transplant (HSCT) with virus-specific, antigen-selected T-cells, selected using the CliniMACS prodigy system.

Secondary Objective(s)

* To describe the safety profile of the infusion of CMV- specific, antigen selected T-cells.
* To describe the toxicities related to infusion of CMV- specific, antigen selected T-cells.
* To describe the rate of eradication of opportunistic CMV infections after HSCT and and treatment with CMV-specific, antigen-selected T-cells using the CliniMACS Prodigy System.

This feasibility study will include a single treatment cohort.

Eligibility criteria: Inclusion Criteria:

* Patients must have received allogeneic hematopoietic stem cell transplant and be greater than 30 days post-transplant at the time of registration
* Patients must have documented opportunistic CMV infection, or reactivation; the criteria include (both of the following criteria must be met)

  * Patients may have asymptomatic viremia (\>1000 copies/ml) OR presence of symptoms secondary to CMV infection, AND
  * Patients must have ONE OF THE NEXT FOUR CRITERIA:

    * Absence of an improvement of viral load after ≥ 14 days of antiviral therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log, i.e. 10-fold) or
    * New, persistent and/or worsening CMV-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 or foscarnet.
    * Second recurrence of CMV viremia, CMV-related symptoms, signs and/or markers of end organ compromise.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
* 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 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.
* Patients with opportunistic viral infections other than CMV.
* Patients with active, grade 2-4, acute graft vs. 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.

Donor eligibility

* Related donor of T cells must be at least partially HLA compatible, matching with recipient in at least 3/6 HLA loci (HLA-A, HLA-B, and HLA-DRB1 loci will be considered for this).
* Must have evidence of a serologic response (i.e. be seropositive) against CMV.
* Age ≥ 18 years
* Must meet the criteria for donor selection defined in the Standard Operating Procedures of University Hospitals Seidman Cancer Center Stem Cell Transplant Program
* Must be capable of undergoing a single standard 2 blood volume leukapheresis or donation of one unit of whole blood

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 100 days after transplant
Secondary outcomes:
measure: Eradication rate of opportunistic CMV infections
timeFrame: Up to 100 days after transplant
measure: response rate
timeFrame: Up to 100 days after transplant
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Mari H Dallas, MD
role: PRINCIPAL_INVESTIGATOR
References: