Combined Infusion of Cytotoxic T-Lymphocytes and Vaccination (CYNTAX)

Combined Infusion of Cytotoxic T-Lymphocytes and Vaccination to Enhance Infection-Specific Immune Reconstitution Post-Allogeneic Stem Cell Transplantation

To assess the safety and biological efficacy of prophylactically administered donor-derived multi-infection specific cytotoxic T lymphocytes (CTLs) (targeting cytomegalovirus (CMV), Adenovirus (Adv), Epstein Barr virus (EBV), Varicella-Zoster virus (VZV), Influenza (Flu), BK virus (BKV), and Aspergillus (Asp)) combined with early immunisation with Influenza and VZV vaccines for the prevention of viral and fungal infection following allogeneic blood or marrow stem cell transplantation.

Study Overview

• Status: Unknown
• Conditions: Complication of Transplant
• Intervention / Treatment: Biological: T-cell infusion, influenza vaccination

Detailed Description

The study will analyse the safety and biological efficacy of administering the investigational products (donor-derived T cells stimulated with viral and fungal antigen expressing DC combined with Flu and VZV immunisation), for the prophylaxis of viral and fungal reactivation and/or infection following allogeneic blood or marrow transplantation. The cells will be given prophylactically a minimum of 28 days after transplantation followed by administration of the Flu and VZV vaccines 24 to 72 hours later. The AIMS are to study the safety of combining CTL infusions and vaccination as well as their effect on reconstitution of infection-specific immunity, viral and Aspergillus reactivation and infection rates after transplantation, viral load, and use of antiviral and antifungal pharmacotherapy for specific infections. The investigators will also evaluate the safety of infusions and vaccinations with respect to the development adverse events within the first 12 months post transplant.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, Sydney, New South Wales, Australia, 2145
      • Westmead Hospital Department of Haematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing myeloablative or non-myeloablative allogeneic transplantation from an HLA (A, B and DR) identical or 1-3 antigen mismatched family or unrelated donor.
• Transplant performed for any type of non-malignant condition or haematological malignancy including but not limited to acute and chronic leukaemia, myelodysplasia, non Hodkgins and Hodgkin lymphoma or myeloma.
• Recipients of peripheral blood or bone marrow stem cells.
• Adequate hepatic and renal function (< 3 x upper limit of normal for AST (SGOT), ALT (SGPT), < 2 x upper limit of normal for total bilirubin, serum creatinine).
• Estimated life expectancy of at least 6 months.
• Patient (or legal representative) has given informed consent

Exclusion Criteria:

• Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks immediately prior to infusion or planned within 4 weeks after infusion.
• Grade II or greater graft versus host disease within 1 week prior to infusion.
• Prednisone or methylprednisone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
• Allergies to eggs or components of the Fluvax or Varivax vaccines.
• Privately insured in or outpatients

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: T-cell infusion; Infusion of donor-derived T cells. Non randomised, prevention study arm	Biological: T-cell infusion, influenza vaccination; Donor derived infection-specific T-cells (with activity against CMV,adenovirus, EBV, VZV, Influenza, BKV and Aspergillus) and vaccination (with Fluvax)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of infection-specific T-cell infusion and vaccination	Presence of acute infusion related toxicities	1 week

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in infection specific immune reconstitution	1 week, 2 weeks, 3 weeks, 4 weeks, 3 months, 6 months, 9 months, 12 months (post T-cell infusion)
Change in CMV, EBV and BKV load based on quantitive PCR	1 week, 2 weeks, 3 weeks, 4 weeks, 3 months, 6 months, 9 months, 12 months (post T-cell infusion)
Use of specific anti-viral pharmacotherapy	12 months (post T-cell infusion)
Use of systemic anti-fungal drugs including amphotericin and azoles	12 months (post T-cell infusion)
Incidences of GVHD	12 months (post T-cell infusion)
Number of in-hospital days following first discharge post transplant	12 months (post T-cell infusion)

Collaborators and Investigators

• Sponsor: University of Sydney
• Investigators: Principal Investigator: David Gottlieb, Professor, Westmead Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: July 22, 2016
• First Posted (Estimate): July 25, 2016

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: infection
• Other Study ID Numbers: Cyntax

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO