Clinical Trial Results:
A Phase 2 open label study to investigate the efficacy of autologous EBV-specific T-cells for the treatment of patients with aggressive extranodal NK/T-cell lymphoma (ENKTCL).
Summary
|
|
EudraCT number |
2013-004380-31 |
Trial protocol |
GB DE |
Global end of trial date |
05 Sep 2018
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
02 Aug 2019
|
First version publication date |
02 Aug 2019
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
CM-2013-01
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01948180 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Cell Medica Inc.
|
||
Sponsor organisation address |
7505 Fannin Street, Suite 200, Houston, United States,
|
||
Public contact |
Clinical Trials Information, Cell Medica Ltd., 0044 02075544070, info@cellmedica.co.uk
|
||
Scientific contact |
Clinical Trials Information, Cell Medica Ltd., 0044 02075544070, info@cellmedica.co.uk
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
05 Sep 2018
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
05 Sep 2018
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
05 Sep 2018
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
To evaluate the overall response rate per independent endpoint assessment.
|
||
Protection of trial subjects |
This study was conducted in accordance with the accepted version of the Declaration of Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, Subpart D, of Title 21 of
the US Code of Federal Regulations (CFR), in compliance with International Council for Harmonisation (ICH) good clinical practice (GCP) guidelines, and according to the appropriate regulatory requirements in the countries where the study was conducted.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 2014
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
30 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 3
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 2
|
||
Country: Number of subjects enrolled |
United States: 7
|
||
Country: Number of subjects enrolled |
United Kingdom: 3
|
||
Worldwide total number of subjects |
15
|
||
EEA total number of subjects |
6
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
12
|
||
From 65 to 84 years |
3
|
||
85 years and over |
0
|
|
||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||
Screening details |
54 subjects screened. 38 of 54 were screening failures. 16 of 54 screened subjects entered treatment phase, 1 died before receiving first dose. Remaining 15 patients were treated with CMD-003. | |||||||||||||||||||||
Period 1
|
||||||||||||||||||||||
Period 1 title |
Treatment Phase (overall period)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
Arm title
|
Group A | |||||||||||||||||||||
Arm description |
Patients with measurable disease according to international consensus standards as defined by the 2014 Lugano Criteria at baseline. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
CMD-003
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection
|
|||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||
Dosage and administration details |
Treatment consisted of 2×107 CD3+ cells/m2 administered on Day 1 and Day 15 as intravenous infusions over a 1 to 10 minute period through either a peripheral or an existing central line. An infusion set with a standard blood filter (pore size no smaller than 170 microns) could be used, per institutional standard operating procedures. To ensure the entire CMD-003 product was infused, the bag was rinsed with a volume of sterile saline solution at the end of the infusion.
|
|||||||||||||||||||||
Arm title
|
Group B | |||||||||||||||||||||
Arm description |
Patients with no measurable disease at baseline. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
CMD-003
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection
|
|||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||
Dosage and administration details |
Treatment consisted of 2×107 CD3+ cells/m2 administered on Day 1 and Day 15 as intravenous infusions over a 1 to 10 minute period through either a peripheral or an existing central line. An infusion set with a standard blood filter (pore size no smaller than 170 microns) could be used, per institutional standard operating procedures. To ensure the entire CMD-003 product was infused, the bag was rinsed with a volume of sterile saline solution at the end of the infusion.
|
|||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group A
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients with measurable disease according to international consensus standards as defined by the 2014 Lugano Criteria at baseline. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group B
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients with no measurable disease at baseline. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Group A
|
||
Reporting group description |
Patients with measurable disease according to international consensus standards as defined by the 2014 Lugano Criteria at baseline. | ||
Reporting group title |
Group B
|
||
Reporting group description |
Patients with no measurable disease at baseline. | ||
Subject analysis set title |
Group A MITT
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
For efficacy endpoints: ORR, CRR, response duration, TTR, and PFS were only presented for patients assigned to Group A (patients with measurable disease) who received at least one dose with a formal response determined at the week 8 visit or later (modified intent-to-treat (MITT) population).
|
||
Subject analysis set title |
Group A/B MITT
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Combined MITT population for group A and B
|
||
Subject analysis set title |
Safety Population Overall
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Overall Safety Population (Group A and Group B)
|
|
|||||||||||
End point title |
Overall Response Rate [1] | ||||||||||
End point description |
Overall Response Rate: The ORR was defined as the percentage of evaluable patients with measurable disease whose best response was either a CR or a PR according to the Lugano 2014 criteria and central independent radiological review
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
12 months
|
||||||||||
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: Due to the small sample size, only a descriptive analysis and documentation of data listings of this endpoint was specified. |
|||||||||||
|
|||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Complete Response Rate | ||||||||||
End point description |
The CRR was defined as the percentage of evaluable patients with measurable disease who experienced a CR, as their best overall response.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
12 months
|
||||||||||
|
|||||||||||
No statistical analyses for this end point |
|
|||||||
End point title |
Duration of Response | ||||||
End point description |
Duration of Response is defined as the response duration time in days from Complete Response or Partial Response until lymphoma progression or death as a result of any cause, whichever occurred first.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Duration of study
|
||||||
|
|||||||
Notes [2] - Median not reached |
|||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Time to Response | ||||||||
End point description |
TTR was defined as the time in days from study entry (Day 1 of CMD-003 dosing) until the precise date of a CR or PR, whichever occurred first. This was applicable only to evaluable patients with measurable disease.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Duration of study
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||
End point title |
Progression-Free Survival | ||||||
End point description |
PFS was defined as the time from study entry until lymphoma progression or death as a result of any cause, whichever occurred first. The date of progression was defined as the first date of documentation of PD.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Duration of study
|
||||||
|
|||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Disease-Free Survival | ||||||||||||
End point description |
DFS was measured from time of occurrence of disease-free state or attainment of a CR to disease recurrence or death, whichever occurred first. Applicable to patients regardless of measurable disease status in the study.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Duration of study
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Overall Survival | |||||||||
End point description |
OS was defined as the time from study entry until death as a result of any cause. This definition was applicable to patients regardless of measurable disease status in the study.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Duration of study
|
|||||||||
|
||||||||||
Notes [3] - Median not reached [4] - Median not reached |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were recorded from the time of first study product dose until 30 days after last study product dose. SAEs were recorded at every study visit for up to one year.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety Population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All subjects treated were considered eligible for safety evaluation. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
20 Mar 2014 |
Principal changes to allow additional salvage therapies, patients with NK/T cutaneous lesions, and to allow patients to receive HSCT after 8-week follow-up. Other changes made for clarification and consistency. |
||
09 Sep 2014 |
Administrative Amendment – Replaced references to Cheson 2007 with 2014 along with corresponding response table in Appendix F. |
||
05 Nov 2014 |
The main areas clarified are exclusion of women of child bearing potential; withdrawals and discontinuations alignment; extend safety monitoring of first few patients immediately post cell administration; addition of 30 month assessment to capture data out to 2 years after last study dose. Various minor edits. |
||
20 Nov 2015 |
Increase starting material volume to 200 mL and provided general guidance for autologous blood donation to promote safe blood collection for the patient. Clarify in-line filtration for IP infusion sets, update prohibited medications to include G-CSF and HDAC inhibitors frequently used in this patient population. Added option for patient’s extra tumor tissue to be tested by centralized pathology lab, when possible. |
||
06 Jun 2016 |
Change screening phase eligibility criteria to exclude patients who have failed 3 or more prior chemotherapy regimens or is considered to have Asparaginase refractory disease and increase life expenctancy to 4 months. Limit treatment phase eligibility to patients with active disease as assessed by imaging, clinical signs or elevated EBV DNA viral load. Also exclude patients with significant liver dysfunction. Allow investigator to decide best salvage treatment option (salvage not mandatory), instead of requiring gemcitabine as the only salvage option, prior to starting CMD-003 treatment. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |