Clinical Trial Results:
A Phase I/II study to investigate the safety of Adenovirus specific T cells given to high-risk paediatric patients post allogeneic haematopoietic stem cell transplant (allo-HSCT) to treat reactivation of adenovirus.
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Summary
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EudraCT number |
2011-001788-36 |
Trial protocol |
GB |
Global end of trial date |
31 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Mar 2017
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First version publication date |
25 Mar 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CM-2011-02
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Additional study identifiers
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ISRCTN number |
ISRCTN22322271 | ||
US NCT number |
NCT01822093 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Cell Medica Ltd.
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Sponsor organisation address |
1 Canal side studios, 8-14 st Pancras way, London, United Kingdom, NW1 0QG
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Public contact |
Medical and Scientific Affairs, Cell Medica Ltd., 44 02075544070, medical@cellmedica.co.uk
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Scientific contact |
Medical and Scientific Affairs, Cell Medica Ltd., 44 02075544070, medical@cellmedica.co.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Dec 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Dec 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety of ADV-specific T cells.
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Protection of trial subjects |
The protocol was designed and the study was conducted in accordance with guidelines for ICH GCP adopted by the European Union under Directive 2005/28/EC which requires that clinical studies are conducted in accordance with ethical Principles outlined in the declaration of Helsinki.
Appropriate consent was obtained from all patients and donors before any protocol related procedures were performed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Nov 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
2
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Children (2-11 years) |
5
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Enrolment period: November 2012 - July 2016 | ||||||||||||
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Pre-assignment
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Screening details |
Paediatric patients that develop ADV infection post allo-HSCT. Patients must meet all inclusion/exclusion criteria and provide consent. | ||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
8 | ||||||||||||
Number of subjects completed |
8 | ||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Cytovir ADV | ||||||||||||
Arm description |
Cytovir ADV Dose 1 (1x10e4/Kg total CD3+ lymphocytes) Cytovir ADV Dose 2 (Maximum target dose 1x10e5/Kg total CD3+ lymphocytes) | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Cytovir ADV
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Investigational medicinal product code |
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Other name |
ADV specific T cells
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Cytovir ADV should be administered at the earliest possible opportunity following identification of ADV infection but not before 28 days post-allo-HSCT.
A single dose of 1x10e4/kg total CD3+ lymphocytes will be infused. There is the option for a secondary maximum target dose of 1x10e5/kg total CD3+ lymphocytes, if the patient has significant ADV viraemia requiring antiviral therapy at ≥ 4 weeks after the first infusion.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who received at least one dose of Cytovir ADV.
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Subject analysis set title |
Per Protocol Analysis Set
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients in the Full Analysis set who completed study assessments up to and including Day 180 (6 months)
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End points reporting groups
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Reporting group title |
Cytovir ADV
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Reporting group description |
Cytovir ADV Dose 1 (1x10e4/Kg total CD3+ lymphocytes) Cytovir ADV Dose 2 (Maximum target dose 1x10e5/Kg total CD3+ lymphocytes) | ||
Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients who received at least one dose of Cytovir ADV.
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Subject analysis set title |
Per Protocol Analysis Set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All patients in the Full Analysis set who completed study assessments up to and including Day 180 (6 months)
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End point title |
Toxicity [1] | |||||||||||||||
End point description |
Incidence and severity of GvHD, cytopenias, Grade 3-4 adverse events
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End point type |
Primary
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End point timeframe |
Up to 6 months following infusion
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were planned or performed. |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Requirement for second infusion | ||||||||||||
End point description |
The number and percentage of patients receiving the second infusion of ADV specific T cells
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End point type |
Secondary
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End point timeframe |
Up to 6 months following infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of treatment days with other anti-infective drugs | ||||||||||||
End point description |
The total number of days that each patient takes any relevant anti-infective medications during the study period
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End point type |
Secondary
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End point timeframe |
Up to 6 months following infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of treatment days with antiviral drugs | ||||||||||||
End point description |
The total number of days that each patient takes any anti-viral medications during the study period
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End point type |
Secondary
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End point timeframe |
Up to 6 months following infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of In-hospital Days | ||||||||||||
End point description |
The number of in-hospital days during the study period
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End point type |
Secondary
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End point timeframe |
Up to 6 months following infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Incidence of AEs, including serious adverse events (SAEs) | ||||||||||||
End point description |
Treatment emergent Adverse Events
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End point type |
Secondary
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End point timeframe |
Up to 6 months following infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Viral clearance | ||||||||||||||||
End point description |
Time to absence of ADV viraemia
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End point type |
Secondary
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End point timeframe |
Up to 6 months following Cytovir ADV infusion
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 6 months following infusion of ADV Specific T cells
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Adverse event reporting additional description |
Treatment-emergent adverse events.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
ADV specific T cells
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Reporting group description |
ADV specific T cells | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Sep 2012 |
Clarification required in protocol regarding how patient treatment is handled including additional clarity around eligibility criteria. |
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24 Apr 2013 |
The study protocol was revised to allow some flexibility with the 2nd dose. The protocol was amended to state that the second dose is a maximum target of 1 x 10e5 CD3+ T cells/ kg (minimum 1 x 10e4/ kg) in order that additional treatment options are always available should a patient require a second dose.
The study protocol was also amended to allow immune reconstitution baseline assays to be avoided in certain circumstances (i.e. severely lymphopaenic patients).
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24 Mar 2014 |
Clarification of IDSMC stopping rules and safety reporting. Patients with GvHD ≥ grade II would be excluded from the study (or dosing delayed until it has resolved) and any cases of de novo GvHD > grade II would be reported to the Independent Data Safety Monitoring Committee (IDSMC). The protocol was updated to clarify recording and reporting of expected safety events. The list of expected events was also updated. |
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27 Aug 2014 |
Study endpoint revised.
Secondary objective (evaluation of persistence and expansion of adoptively transferred ADV-specific T cells) changed to an exploratory endpoint. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
