NCT02510404

Treatment of EBV, CMV, and Adenovirus Infections in Primary Immunodeficiency Disorders With Viral-specific Cytotoxic T-Lymphocytes

Completed Phase 1 Last updated 15 January 2020

What this trial tests

Phase 1 trial testing mCTLs in Refractory Viral Infections in 1 participant. Completed in 8 June 2019.

Timeline

1 April 2014

Primary endpoint
8 May 2019

8 June 2019

Quick facts

Lead sponsor	Catherine Bollard
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	1
Start date	1 April 2014
Primary completion	8 May 2019
Estimated completion	8 June 2019
Sites	1 location across United States

Drugs / interventions tested

• mCTLs — full drug profile →

Conditions studied

• Refractory Viral Infections — all drugs for Refractory Viral Infections →

Sponsor

Catherine Bollard — full company profile →

Who can join

Adults 4 Weeks to 45, any sex, with Refractory Viral Infections. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Assessments of patients with adverse events after mCTLs infusion
  Time frame: 45 days
  The safety endpoint will be defined as acute GvHD grades III-IV related to the T cell product within 45 days of the last VST dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE)

Sponsor's own description

PIDD represent an expanding group of genetic disorders that compromise immunity against bacteria, viruses, and fungi. The most severe forms of PIDD cause profound susceptibility to opportunistic infections due to impaired or absent T-cell immunity. These diseases can be rapidly fatal unless treated via hematopoietic stem cell transplantation (HSCT). Chronic viral illnesses are a common presenting feature of many of these disorders, and studies have shown that survival of HSCT is profoundly impacted by the patient's pre-transplant disease status. Primary infections with viruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common, and respiratory viruses such as adenovirus also frequently cause infection. In patients with severe combined immunodeficiency (SCID), a prior study identified these viruses as the most common causes of mortality in the immediate period following HSCT. Though some forms of PIDD are amenable to HSCT without requiring conditioning chemotherapy, many forms require a variable degree of pre-conditioning to ensure that stable engraftment of the donor cells is achieved. The administration of cytotoxic chemotherapy used in the conditioning regimens can however increase the risk for regimen related toxicity and for some patients (especially those with active viral infections) this risk is particularly high, leading to high treatment related mortality rates. For these reasons, many such patients are not even considered candidates for HSCT or are delayed getting to HSCT and ultimately succumb to infection before they can receive the transplant.

The primary objective of this study is to determine the safety of administering third-party multivirus-specific cytotoxic T lymphocytes (mCTL) from adult CMV seropositive donors to treat refractory viral infections in patients with primary immunodeficiency disorders (PIDD) prior to hematopoietic stem cell transplantation (HSCT).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Virus-specific T-cell therapies for patients with primary immune deficiency.
   Keller MD, Bollard CM. · · 2020 · cited 50× · PMID 31942610 · DOI 10.1182/blood.2019000924
2. CMV Prevention and Treatment in Transplantation: What's New in 2019.
   Stern A, Papanicolaou GA. · · 2019 · cited 23× · PMID 31732823 · DOI 10.1007/s11908-019-0699-0