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25BT056: Basket Study of Viral Cytotoxic T Lymphocytes

ConditionsEBV ViremiaCMV ViremiaBK ViremiaAdenovirusPost-transplant Lymphoproliferative DisorderViremiaCytomegalovirus EnteritisAdenovirus InfectionEpstein-Barr Virus Infection ReactivationEpstein Barr Virus InfectionBK Virus InfectionRefractory Viral InfectionOpportunistic Viral InfectionPrimary ImmunodeficiencySevere Combined Immunodeficiency (SCID)Inherited Immunodeficiency DiseasesAcquired ImmunodeficiencyStem Cell Transplant ComplicationsSolid Organ Transplant Complications
Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age0-29
SponsorChildren's Hospital of Philadelphia

About this trial

This study is evaluating the safety and effectiveness of virus-specific cytotoxic T lymphocytes (vCTLs) for treating difficult-to-control viral infections caused by cytomegalovirus (CMV), adenovirus (ADV), Epstein-Barr virus (EBV), or BK virus in children, adolescents, and young adults with weakened immune systems. Eligible participants include recipients of hematopoietic stem cell transplantation, solid organ transplantation, and patients with primary immunodeficiency disorders.

vCTLs are immune cells collected from a related donor and selected to recognize and fight specific viruses. The cells are manufactured using the CliniMACS® Cytokine Capture System and administered by intravenous infusion. Additional infusions may be given if viral infection persists.

The study will assess the safety of vCTL therapy, including the risk of graft-versus-host disease (GVHD) and infusion-related reactions, as well as its ability to reduce viral infection, improve clinical outcomes, and support survival. Participants will be monitored for approximately 12 weeks after their final vCTL infusion. Participants will all receive vCTLs; there is no comparison group.

Participants will:

1. Have donor-derived vCTLs manufactured for infusion using the CliniMACS Cytokine Capture System 2. Receive the vCTLs through an intravenous infusion 3. Be monitored for side effects and infusion reactions, viral levels through blood testing, clinical outcomes, including response to treatment, survival, and time without detectable virus

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Increasing viremia by quantitative PCR with increase from baseline over 7 days, or persistent detection after 14 days despite appropriate standard of care therapy (e.g. anti-viral therapy, withdrawal of immunosuppression), AND/OR

Progressive symptomatic viral infection evidenced by persistent clinical symptoms or end-organ disease attributable to the viral infection that has not improved after at least 7 days of appropriate standard-of-care therapy, or develops new clinical manifestations despite standard-of-care therapy, AND/OR

Antiviral resistance, or inability to receive appropriate antiviral therapy due to intolerance, toxicity, contraindication, or lack of a feasible antiviral treatment option.

Age 0 - 29 years at time of consent

Disqualifiers

Subjects with ≥ Grade 2 acute GVHD or moderate to severe chronic GVHD at the time of vCTL infusion

Subjects receiving systemic steroids (> 0.5mg/kg/day prednisolone equivalent) at the time of vCTL infusion

Receipt of donor lymphocyte infusion within the 4 weeks preceding vCTL infusion

Receipt of thymoglobulin, alemtuzumab, or other T cell immunosuppressive monoclonal antibody within the 4 weeks preceding vCTL infusion

Trial design

Design model

Single group

Treatments tested in this trial

  • Virus-Specific Cytotoxic T Lymphocytes (vCTLs)

    Biological/Vaccine

    Donor-derived virus-specific cytotoxic T lymphocytes (vCTLs) targeting one or more of cytomegalovirus (CMV), adenovirus (ADV), Epstein-Barr virus (EBV), and BK virus. Cells are manufactured using the CliniMACS® Prodigy and CliniMACS Cytokine Capture System (IFN-γ) following stimulation with virus-specific PepTivator® peptide pools. vCTLs are administered by IV infusion at a dose of 2-3 × 10\^4 CD3+ cells/kg recipient weight for HLA-matched related donors or 0.4-0.6 × 10\^4 CD3+ cells/kg recipient weight for HLA-mismatched related donors. Additional infusions of the same dose may be administered every 2 weeks in subjects with ongoing clinically significant viral infection who continue to meet infusion eligibility criteria, for up to 5 total infusions. The intervention is intended for treatment of refractory viral infections in patients with inherited or acquired immunodeficiencies, including recipients of hematopoietic stem cell transplant.

Treatment groups

35 Participants
are divided into 1 treatment group
Group A: Virus-Specific Cytotoxic T Lymphocytes (vCTLs)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Occurrence of Grade 3 or higher acute graft-versus-host disease (GVHD)

This outcome measures the number of participants who develop Grade 3 or higher acute graft-versus-host disease that is assessed as possibly, probably, or definitely related to vCTL infusion. Acute GVHD will be graded using the Center for International Blood and Marrow Transplant Research (CIBMTR) criteria.

Time frame
From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
2

Occurrence of Grade 3 or higher infusion-related reactions

This outcome measures the number of participants who experience a Grade 3 or higher infusion-related reaction that is assessed as possibly, probably, or definitely related to vCTL infusion. Infusion-related reactions will be graded using NCI CTCAE version 6.0.

Time frame
From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion

Secondary outcomes

1

Cytomegalovirus (CMV) Overall Response Rate

This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.

Time frame
Two weeks after the final vCTL infusion
2

Adenovirus (ADV) Overall Response Rate

This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.

Time frame
Two weeks after the final vCTL infusion
3

Epstein Barr Virus (EBV) Overall Response Rate

This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.

Time frame
Two weeks after the final vCTL infusion
4

BK polyomavirus (BKV) Overall Response Rate

This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.

Time frame
Two weeks after the final vCTL infusion

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Children's Hospital of Philadelphia

Lead sponsor

Source ClinicalTrials.gov

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