Virus-specific ImmunoTherapy Following Allogeneic Stem Cell Transplantation

NCT ID: NCT02702427

Last Updated: 2019-05-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-03
• Study Completion Date: 2019-04-01

Brief Summary

Invasive infections with CMV and Adenovirus, not responding to virostatic treatment are treated with virusspecific donor derived or autologous virusspecific T-cells.

Detailed Description

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment option for several haematological diseases. In spite of substantial progress in this field, viral infections, mainly cytomegalovirus (CMV) and adenovirus (HAdV) in the context of delayed immunoreconstitution remain life threatening complications. Weekly screening of high-risk patients and preemptive virostatic treatment has become a current strategy. Unfortunately, treatment with virostatic drugs is associated with substantial nephro- and myelo-toxicity and of limited effectiveness. Human adenovirus (HAdV) and cytomegalvirus (CMV) disseminated infections are associated with mortality rates of up to 50%-60% despite virostatic treatment.

All HSCT patients at the St. Anna Children's Hospital undergo weekly viral quantitative PCR-screening for HAdV and CMV and weekly PB FACS (Fluorescence Activated Cell Sorter)-Analysis according to the local HSCT-diagnostic SOP (Standard Operating Procedure) from day -7 until day +100 Patients with HAdV or CMV viremia will receive preemptive treatment with either gancyclovir (in case of isolated CMV-viremia) or Cidofovir (in case of HAdV viremia or combined HAdV/CMV infection). In case of increasing viremia ≥ 1log despite antiviral treatment for two weeks or stable with 10E6 viral load and the absence of virus specific T-cells in the recipient, the treating physician will check, if the patient is eligible for seVirus-T-cell infusion (see inclusion criteria).

Study Design: Mononuclear Donor-Cells from peripheral blood (100 ml extra donation) will be cryopreserved at the time-point of HSCT. In case of progredient viremia these cells will be stimulated with interleukin-15 and peptides out of the virus molecule, virusspecific T-Cells are enriched for 2-3 logs-teps and potentially alloreactive cells diluted at the same time. This new approach reduces the risk of graft-versus-host-disease (GvHD) and enables the infusion of virus-specific T-cells also from haploidentical donors.

Conditions

Cytomegalovirus Infection; Adenovirus Infection

Study Design

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

Study Groups

ARM 1

Patients with Adenovirus or CMV infection after HSCT and no reduction of viral disease or stable disease with 10E6 viral copies within 2 weeks of antiviral treatment will receive a single infusion of virus-specific T-Cells

Group Type: EXPERIMENTAL

virus-specific T-Cells

Intervention Type: BIOLOGICAL

infusion

Interventions

virus-specific T-Cells

infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age at timepoint of HSCT ≤18 years undergoing allogeneic stem cell transplantation
• Presence of HAdV or CMV-specific T-cells in the donor or CMV-specific T-cells in the recipient pre-transplant
• Stable (≥ 10E6) or increasing viremia despite antiviral treatment post HSCT
• Absence of HAdV or CMV -specific T cells post HSCT
• Karnofsky / Lansky score >50%
• Pregnancy excluded
• Informed study participation consent is signed

Exclusion Criteria

• Infusion of polyclonal or monoclonal T-cell directed antibodies within 28 days before seVirus T-Cell infusion
• Multiple organ failure at screening-timepoint seVirus T-Cell infusion
• History of GvHD Gr III-IV or actual GvHD Gr III-IV
• Pregnancy
• Treatment with granulocyte transfusion within the last 72 hours
• Karnofsky / Lansky score <50%
• Subject is unwilling or unable to comply with the study procedures
• High dose treatment with steroids (≥ 2mg/kg/d, methylprednisone-equivalent)

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Anna Kinderkrebsforschung

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susanne Matthes, MD

Role: PRINCIPAL_INVESTIGATOR

St. Anna Kinderkrebsforschung

Locations

St. Anna Children's Hospital

Vienna, , Austria

Countries

Austria

Other Identifiers

Eudra CT2013-002492-17

Identifier Type: -

Identifier Source: org_study_id