Clinical trial NCT05075837: Adoptive T-cell Therapy for Resistant Viral Infections After Allogeneic HSCT
Official title: Virus-specific T-cell Immunity for the Treatment of Some Resistant Viral Infections After Allogeneic Hematopoietic Stem Cell Transplantation(HSCT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Viral Infection After HSCT
Keywords: CMV
adenovirus
EBV
adoptive T cell therapy
allogeneic hematopoietic stem cell transplantation
Lead sponsor: Istituto Giannina Gaslini
Sponsor class: OTHER
First posted: 2021-10-13
Enrollment: 10
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase I, open-label, single-arm, non-randomized study, monocentric.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

* Allogeneic transplant with any cells source and conditioning regimen
* Age between 0-21 years
* Viral infection/reactivation (CMV, EBV, ADV)
* Resistance of viral infections to treatments
* Absence of concomitant severe uncontrolled infections
* Life expectancy exceeding 30 days
* Absence of acute or chronic uncontrolled Graft versus Host Disease (GvHD)
* Absence of acute kidney damage (creatinine value\> 3 times the value normal with respect to age) not related to viral infection;
* Absence of severe acute liver injury (direct bilirubin\> 3mg / dl or glutamic-oxaloacetic transaminase -SGOT\> 500 UI/L) not related to viral infection;
* Presence of informed consent to the treatment of the patient / parent /legal guardian.

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

Primary outcomes:
measure: Adverse events
timeFrame: from day +1 of infusion until day +56
Secondary outcomes:
measure: Specific cell viral immunity
timeFrame: from day +1 of infusion until day +56
measure: Variation of viremia
timeFrame: from day +1 of infusion until day +56
measure: Organ damage
timeFrame: from day +1 of infusion until day +56
measure: Overall survival
timeFrame: from day +56 to 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Istituto G. Gaslini
name: Maura Faraci, MD
role: PRINCIPAL_INVESTIGATOR
References: