Combined Infusion of Cytotoxic T-Lymphocytes and Vaccination

Phase 1

• Conditions: Complication of Transplant
• Interventions: Biological: T-cell infusion, influenza vaccination

• Registration Number: NCT02843321
• Lead Sponsor: University of Sydney

Brief Summary

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.

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 Timeline

• Study Start: 2012-08
• Study First Submitted: 2016-05-18
• Study First Submitted QC: 2016-07-22
• Study First Posted: 2016-07-25
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-21
• Last Update Posted: 2016-11-22
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
T-cell infusion	T-cell infusion, influenza vaccination	Infusion of donor-derived T cells. Non randomised, prevention study arm

Primary Outcome Measures

Name	Time	Method
Safety of infection-specific T-cell infusion and vaccination	1 week	Presence of acute infusion related toxicities

Secondary Outcome Measures

Name	Time	Method
Use of systemic anti-fungal drugs including amphotericin and azoles	12 months (post T-cell infusion)
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)
Use of specific anti-viral pharmacotherapy	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)
Number of in-hospital days following first discharge post transplant	12 months (post T-cell infusion)
Incidences of GVHD	12 months (post T-cell infusion)

Trial Locations

Locations (1)

Westmead Hospital Department of Haematology; 🇦🇺 Westmead, Sydney, New South Wales, Australia