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Trial record 3 of 11 for:    r3 stem cell

Partially HLA-matched Third Party Antigen Specific T-cells for Infection Post-stem Cell or Solid Organ Transplantation (R3ACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02779439
Recruitment Status : Unknown
Verified July 2016 by David Gottlieb, University of Sydney.
Recruitment status was:  Recruiting
First Posted : May 20, 2016
Last Update Posted : July 21, 2016
Sponsor:
Information provided by (Responsible Party):
David Gottlieb, University of Sydney

Tracking Information
First Submitted Date  ICMJE May 18, 2016
First Posted Date  ICMJE May 20, 2016
Last Update Posted Date July 21, 2016
Study Start Date  ICMJE January 2013
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2016)
Infusion related safety [ Time Frame: 1 week ]
infusion related adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Partially HLA-matched Third Party Antigen Specific T-cells for Infection Post-stem Cell or Solid Organ Transplantation
Official Title  ICMJE Therapeutic Infusion of Partially HLA-matched Third Party Donor-derived Virus- and Fungus Specific T-lymphocytes in Patients With Active Viral or Fungal Infection Post-allogeneic Stem Cell or Solid Organ Transplantation
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.
Detailed Description

The study will analyse the safety and biological efficacy of administering the investigational products (most closely HLA-matched third party donor-derived T cells stimulated with viral or fungal antigen expressing DC), for the treatment of viral reactivation and/or infection or fungal infection following allogeneic blood or marrow or solid organ transplantation. The cells will be given therapeutically after transplantation in patients with active viral reactivation or proven/probably fungal infection despite standard therapy.

Our AIMS are to study the safety of third party donor-derived CTL infusions, their effect on treatment of viral reactivation as well as their effect on reconstitution of virus- and fungus-specific immunity, viral and fungal infection and reactivation rates after transplantation, viral load, and use of antiviral and antifungal pharmacotherapy.

We will evaluate the safety of infusions with respect to the development of adverse events within the first 12 months post-CTL infusion and the dynamics of cell persistence by T-cell chimerism analysis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • CMV Infection
  • EBV
  • Adenovirus
Intervention  ICMJE Biological: Virus specific CTLs
Virus specific CTLs will be given to patients with persistent or recurrent viral reactivation after 2 weeks of standard anti-viral therapy
Other Name: T cells
Study Arms  ICMJE Experimental: 3rd party CTL infusion
Virus specific CTLs
Intervention: Biological: Virus specific CTLs
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 18, 2016)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2018
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

  • 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)
  • ECOG status 0 to 3 or Lansky score 30-100
  • 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 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02779439
Other Study ID Numbers  ICMJE R3ACT
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party David Gottlieb, University of Sydney
Study Sponsor  ICMJE University of Sydney
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Sydney
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP