Adoptive T-cell Therapy for Resistant Viral Infections After Allogeneic HSCT (VS-TC)

Virus-specific T-cell Immunity for the Treatment of Some Resistant Viral Infections After Allogeneic Hematopoietic Stem Cell Transplantation(HSCT)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Viral Infection After HSCT
• Intervention / Treatment: Biological: Virus -specific T cells

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Maura Faraci, MD; Phone Number: 01056362405; Email: maurafaraci@gaslini.org
• Study Contact Backup: Name: Stefano Giardino, MD; Phone Number: 01056362405; Email: stefanogiardino@gaslini.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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)

Biological: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	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)	from day +1 of infusion until day +56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific cell viral immunity	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	from day +1 of infusion until day +56
Variation of viremia	To evaluate viremia variations with the measurement of viral PCR after the infusion of virus-specific T lymphocytes evaluated regularly 2 times a week.	from day +1 of infusion until day +56
Organ damage	To report any clinical and/or laboratory changes related to the viral infection	from day +1 of infusion until day +56
Overall survival	To evaluate the overall survival (OS) after virus-specific T lymphocytes	from day +56 to 12 months

Collaborators and Investigators

• Sponsor: Istituto Giannina Gaslini
• Investigators: Principal Investigator: Maura Faraci, MD, Istituto G. Gaslini

Study record dates

Study Major Dates

• Study Start (Estimated): February 27, 2024
• Primary Completion (Estimated): July 25, 2024
• Study Completion (Estimated): July 25, 2025

Study Registration Dates

• First Submitted: September 21, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: adenovirus; CMV; EBV; allogeneic hematopoietic stem cell transplantation; adoptive T cell therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Virus Diseases
• Other Study ID Numbers: IGianninaGaslini

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD are to be shared with hematologists and oncologists of our Institute

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No