Partially HLA-matched Third Party Antigen Specific T-cells for Infection Post-stem Cell or Solid Organ Transplantation

NCT02779439 | Unknown Phase 1

• 1 other identifier: R3ACT
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the safety and biological efficacy of therapeutically administered most closely HLA-matched third party donor-derived specific cytotoxic T lymphocytes (CTLs) targeting cytomegalovirus (CMV) or Adenovirus (Adv) or Epstein Barr virus (EBV) or fungi including Aspergillus and Candida species for the treatment of viral infection following allogeneic blood or marrow stem cell or solid organ transplantation.

Conditions

CMV Infection; EBV; Adenovirus

Outcome Measures

Primary Outcomes (1)

• Infusion related safety

  infusion related adverse events

  1 week

Study Arms (1)

3rd party CTL infusion

EXPERIMENTAL

Virus specific CTLs

Biological: Virus specific CTLs

Interventions

Virus specific CTLs BIOLOGICAL

Virus specific CTLs will be given to patients with persistent or recurrent viral reactivation after 2 weeks of standard anti-viral therapy

Also known as: T cells

3rd party CTL infusion

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipients of myeloablative or non-myeloablative allogeneic or solid organ transplantation for any indication.
• Presence of viral reactivation or infection with CMV, Adv or EBV or invasive fungal disease must be present at the time of infusion as determined by:
• For CMV CMV detectable by antigen detection, PCR or culture in peripheral blood or tissue biopsy or by immunohistochemical staining on tissue biopsy specimen
• For Adv Presence of Adv as detected by PCR, antigen detection or culture in body fluids including blood, stool, urine or nasopharyngeal secretions
• For EBV Elevated EB virus detectable in peripheral blood by PCR or Presence of documented EBV related PTLD diagnosed by tissue biopsy or Elevated EB virus detectable in the blood by PCR and clinical or imaging findings consistent with EBV lymphoma
• For invasive fungal disease Proven or probable invasive fungal disease according to De Pauw 2008\[114\]
• Failure of standard therapy as defined by:
• For CMV The continued presence of detectable CMV virus or antigen after at least 14 days of antiviral therapy with IV ganciclovir or foscarnet Recurrence of detectable CMV virus or antigen after at least 2 weeks of prior antiviral therapy
• For Adv A rise or less than 50% reduction in viral load in blood or any site of disease as measured by PCR or any quantitative assay despite use of therapy as determined by the treating physician; Standard therapy may include intravenous cidofovir within the limits of renal function
• For EBV Increase or less than 50% decrease in the size of EBV lymphoma or
• Increase or less than 50% decrease in the EBV viral load in peripheral blood despite use of appropriate therapy as determined by the treating physician which may include:
• Reduction in immunosuppression
• Rituximab 375mg/m2 up to 4 infusions
• Cytotoxic chemotherapy
• o For invasive fungal disease inadequate or incomplete clinical response according to treating physician after at least 5 days of best available therapy

You may not qualify if:

• 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 methylprednisolone at a dose of \> 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
• ECOG status 4 or Lansky score \<30
• Privately insured in or outpatients in New South Wales participating centres (see 12.5 Indemnity issues).

Sponsors & Collaborators

• University of Sydney: lead

Study Sites (1)

Westmead Hospital

Sydney, New South Wales, 2145, Australia

RECRUITING

Related Publications (1)

• Withers B, Blyth E, Clancy LE, Yong A, Fraser C, Burgess J, Simms R, Brown R, Kliman D, Dubosq MC, Bishop D, Sutrave G, Ma CKK, Shaw PJ, Micklethwaite KP, Gottlieb DJ. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. Blood Adv. 2017 Nov 2;1(24):2193-2205. doi: 10.1182/bloodadvances.2017010223. eCollection 2017 Nov 14.

  PMID: 29296867 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Central Study Contacts

David Gottlieb, MD FRACP

CONTACT

david.gottlieb@sydney.edu.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor David Gottlieb

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: May 20, 2016
• Study Start: January 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: March 1, 2018
• Last Updated: July 21, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)