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Adoptive T-cell Therapy for Resistant Viral Infections After Allogeneic HSCT

Phase 1
Not yet recruiting
Conditions
Viral Infection After HSCT
Interventions
Biological: Virus -specific T cells
Registration Number
NCT05075837
Lead Sponsor
Istituto Giannina Gaslini
Brief Summary

The aim of the study is to evaluate the adverse events and the efficacy of virus specific T lymphocytes selected in vitro from a family donor to treat some refractory viral infections as Adenovirus (ADV), Ebstein Barr virus (EBV), Cytomegalovirus (CMV) that developed in young patients (age between 0 and 21 years) after allogeneic hematopoietic cell transplantation (allo-HSCT) performed at the Transplant Clinical Unit of the IRCCS G. Gaslini Institute (IGG).

Detailed Description

The rationale for the study is based on the evidence that, despite the progress obtained in the management and prevention of viral infections in the patients who received allo-HSCT, some viral infections continue to be severe complications that may occurred before the immune recovery. Some of these viral reactivations are not responsive to the first or second line treatment and their treatment may be represent an important issue. The adoptive cellular immunotherapy based on the infusion of virus-specific T lymphocytes represent a valid therapeutic option and the quick access to this cellular therapy is crucial to prevent severe organ complications related to viral infection. In this study, the use of virus-specific T lymphocytes obtained from a seropositive family donor, briefly activated in vitro and immunomagnetically captured by their capacity to secrete IFN-gamma allows to obtain a rapidly usable T-lymphocyte population (both CD4+ and CD8+) potentially able to expand into the patient. The effectiveness, safety (peptides used are synthetic, no animal components, closed system production), good tolerance and speed of modality (less than 36 hours for production) is reported by many clinical studies.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
10
Inclusion Criteria

Not provided

Exclusion Criteria
  • Absence of a suitable donor (seronegativity for the virus in question and / or failure to respond to the secretion test)
  • Patient with severe renal and/or hepatic impairment as specified above
  • Primary or secondary graft failure
  • Relapse of malignant underlying disease

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Virus-specific T cells for the treatment of active viral infections following allogeneic HSCT.Virus -specific T cellsVirus specific T lymphocytes selected in vitro from a family donor to treat some refractory viral infections as Adenovirus (ADV), Ebstein Barr virus (EBV), Cytomegalovirus (CMV) that developed in young patients (age between 0 and 21 years) after allogeneic hematopoietic cell transplantation (allo-HSCT)
Primary Outcome Measures
NameTimeMethod
Adverse eventsfrom day +1 of infusion until day +56

To collect any adverse event defined as any significant alteration of vital signs and / or organ function, expressed in clinical, hematochemical and radiological findings according to version 5 of the Common Terminology Criteria for Adverse Events (CTCAE)

Secondary Outcome Measures
NameTimeMethod
Specific cell viral immunityfrom day +1 of infusion until day +56

To evaluate the specific cell viral immunity for some virus defined as presence and number of CD3 + IFN-gamma + lymphocytes count in the patient's peripheral blood

Variation of viremiafrom day +1 of infusion until day +56

To evaluate viremia variations with the measurement of viral PCR after the infusion of virus-specific T lymphocytes evaluated regularly 2 times a week.

Organ damagefrom day +1 of infusion until day +56

To report any clinical and/or laboratory changes related to the viral infection

Overall survivalfrom day +56 to 12 months

To evaluate the overall survival (OS) after virus-specific T lymphocytes

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