Clinical Grade Adenovirus Specific T Cells for Immunotherapy After Allogeneic Stem Cell Transplantation (CTL-ADV)

Phase 1

Completed

• Conditions: Adenovirus Infection

• Registration Number: NCT02851576
• Lead Sponsor: Central Hospital, Nancy, France

Brief Summary

Fourteen patients will be included for infusion of adenovirus-specific T-cells generated by a clinical grade IFN-γ based immunomagnetic isolation from a leukapheresis from their original donor or a haploidentical donor, in case of Umbilical cord blood transplantation, in the event of refractory ADV infection or disease.

Detailed Description

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) has improved over the last decades. However, after HSCT and especially with matched unrelated, cord blood or haploidentical donors, patients often experience a deep immunodeficiency, increasing susceptibility to viral infections. Among them, adenovirus (ADV) systemic infection, often refractory to antiviral treatment, is associated with a high mortality rate up to 50% (even more in children). Viremia monitoring after HSCT has contributed to improve survival allowing the implementation of a pre-emptive anti-viral treatment before any appearance of clinical signs of ADV disease. Nevertheless, no anti-viral drug is authorized for ADV infections, although intravenous (IV) cidofovir seemed to be, up to now, the most efficient. However, nephrotoxicity, especially tubular dysfunction, is often described, requiring hydratation and uroprotection with probenecid and limiting the treatment period.

Meanwhile, adoptive transfer of ADV-specific T cells, prepared with an immunomagnetic clinical grade technology, is becoming an alternative treatment that has already proved feasible, safe and helpful in viral clearance and immune reconstitution related to an in vivo expansion of ADV-specific T cells leading to clinical improvement (Feuchtinger et al, 2006, 2015; Qazim et al, 2013). Our team proposes a multicenter Phase I/II clinical trial with ADV-specific T cells where 14 patients, with refractory ADV infection or disease after unrelated Peripheral blood or umbilical cord blood HSCT, are included.

Study Timeline

• Study Start: 2011-08
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Study First Submitted: 2016-07-28
• Study First Submitted QC: 2016-07-28
• Study First Posted: 2016-08-01
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-13
• Last Update Posted: 2016-09-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

• Study Population : adults or children
• Allogeneic hematopoietic stem cell (bone marrow and peripheral blood stem cell, umbilical cord blood (UCB))
• sibling or matched unrelated donors 10/10 or 9/10 ((M)MUD) or haploidentical donor in case of UCB transplantation

Within 18 months after HSCT, occurrence of:

• An adenovirus infection without clinical symptoms (except fever with unknown origin) definitively due to this infection, after treatment failure during at least 2 weeks with Cidofovir (5 mg/kg/week).

To determine ADV infection, 2 consecutive viremia performed at 4 days interval must be higher than viral threshold of 500 copies/mL (with significant increase between these 2 analysis and at least 0, 5 log when the first viremia is equal to 500 cp/mL).

• Probable or definitive adenovirus infection after Cidofovir treatment failure, 5 mg/kg/week (according to Wisconsin's criteria)
• and/or renal toxicity or major intolerance to anti-viral drug
• and/or in case Cidofovir is not available in France
• Acute or Chronic GVHD with acute form grade II or less, controlled after 2 lines of treatment at the most.

Or controlled Chronic GVHD

• Life expectancy > 1 month at the time of inclusion

Exclusion Criteria

• Graft failure
• Derogatory HSCT
• Acute or Chronic GVHD in acute form with grade > II, uncontrolled after 2 lines of immunosuppressive agents.
• Patients with grade > III clinical or biological toxicities (according to OMS classification)
• Chronic GVHD uncontrolled
• Immediate life-threatening
• Patients have not signed informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Graft Versus Hot Disease (GVHD) grade >2	1 month	No occurrence of acute Graft Versus Hot Disease (GVHD) grade \>2 and/or extensive chronic GVHD and no reactivation or worsening of acute or chronic GVHD during the first month following infusion.

Secondary Outcome Measures

Name	Time	Method
Follow-up of anti-ADV immune response	90 days	Follow-up of anti-ADV immune response in the recipient (developing a specific immune response based on in vivo CTL expansion evaluated by IFN ELISPOT or intracellular cytokine staining).
Follow-up of ADV viral load	90 days	Follow-up of ADV viral load by quantitative Polymerase Chain Reaction (PCR) : Decrease \> 0.5 Log

Trial Locations

Locations (1)

Centre Hospitalier Universitaire de Nancy; 🇫🇷 Vandœuvre-Lès-Nancy, France