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

NCT ID: NCT05075837

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-27
• Study Completion Date: 2025-07-25

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.

Conditions

Viral Infection After HSCT

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Virus-specific T cells for the treatment of active viral infections following allogeneic HSCT.

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)

Group Type: EXPERIMENTAL

Virus -specific T cells

Intervention Type: BIOLOGICAL

The product is obtained by leukapheresis of a family donor responsive to the virus: consists of virus- specific T lymphocytes (both CD4+ and CD8+) resuspended in PBS / EDTA buffer plus 0.5% Albumin Human. The productive process lasts two consecutive days and includes two phases: a brief activation with specific viral peptide followed by immunomagnetic separation using the CliniMACS® CCS (IFNγ) capture system which allows a fast and automated separation of IFNγ secreting lymphocytes

Interventions

Virus -specific T cells

The product is obtained by leukapheresis of a family donor responsive to the virus: consists of virus- specific T lymphocytes (both CD4+ and CD8+) resuspended in PBS / EDTA buffer plus 0.5% Albumin Human. The productive process lasts two consecutive days and includes two phases: a brief activation with specific viral peptide followed by immunomagnetic separation using the CliniMACS® CCS (IFNγ) capture system which allows a fast and automated separation of IFNγ secreting lymphocytes

Intervention Type: BIOLOGICAL

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Giannina Gaslini

OTHER

Sponsor Role: lead

Responsible Party

Maura Faraci

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maura Faraci, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto G. Gaslini

Central Contacts

Maura Faraci, MD

Role: CONTACT

maurafaraci@gaslini.org

01056362405

Stefano Giardino, MD

Role: CONTACT

stefanogiardino@gaslini.org

01056362405

Other Identifiers

IGianninaGaslini

Identifier Type: -

Identifier Source: org_study_id