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Treatment of EBV, CMV, and Adenovirus Infections in Primary Immunodeficiency Disorders With Viral-specific Cytotoxic T-Lymphocytes
Sponsor study identifier
interventional
1
1 country
1
Study Start
April 2014
Actual (reported)Primary Completion
May 8, 2019
Actual (reported)Study Completion
June 8, 2019
Actual (reported)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).
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
June 8, 2019
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
April 2014
Actual (reported)July 13, 2015
Actual (reported)July 29, 2015
Actual (reported)May 8, 2019
Actual (reported)June 8, 2019
Actual (reported)Assessments of patients with adverse events after mCTLs infusion
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)
45 days
Assessments of viral load response to the mCTLs infusion
12 months
Assessments of Antiviral Immunity
12 months
The investigator will use 3 different dose levels starting with 5 x 106 (a T cell number more than an order of magnitude lower than that administered at the time of an unmanipulated marrow infusion), followed by 1 x 107 and a final dose 2 x 107 mCTLs/m2. They will give the option of administering 2 additional doses (at the same level) of the same or different cell lines, 28 days after the first dose, in subjects that have limited or no improvement in viral count after one dose in the absence of any toxicities attributable to the infusion,or who receive other therapy that may affect the persistence or function of the infused mCTLs.
The investigators have elected to limit this phase I study to PIDD patients with active viral infections unable to be controlled with standard pharmacotherapy, who are therefore likely to benefit from mCTLs treatment. This trial will be performed as dose-escalation study. Patients will be evaluated for matched lines from a bank of third-party mCTLs, derived from CMV seropositive donors. These lines will have been used clinically in prior clinical trials, with safety demonstrated in the post-HSCT setting.
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Childrens National Medical Center
Washington D.C., District of Columbia, 20010, United States
Catherine Bollard, MD
Children's National Research Institute
1 participants (actual enrollment reported by the registry).
First Submitted
July 13, 2015
First Posted
July 29, 2015
Study Start
April 2014
Actual (reported)Contact the study team to confirm eligibility.
Primary Completion
May 8, 2019
Actual (reported)Study Completion
June 8, 2019
Actual (reported)Last Updated
January 18, 2020
Record last verified: 2020-01
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Source: ClinicalTrials.gov.
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