Clinical Trial Results:
Full title of the trial: Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-derived Ex Vivo Expanded Stem and Progenitor Cells, in Adolescents and Adult Patients with Hematological Malignancies
Summary
|
|
EudraCT number |
2014-000074-19 |
Trial protocol |
ES IT NL |
Global end of trial date |
29 Jun 2018
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
12 Jul 2019
|
First version publication date |
12 Jul 2019
|
Other versions |
|
Summary report(s) |
Synopsis |
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 |
GCP#03.01.020
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01816230 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Gamida Cell Ltd.
|
||
Sponsor organisation address |
Beit Ofer, 5 Nahum Hafzadi, Jerusalem, Israel, 9548401
|
||
Public contact |
Kelly Myers, Gamida Cell Ltd, 972 26595631, kelly@gamida-cell.com
|
||
Scientific contact |
Kelly Myers, Gamida Cell Ltd, 972 26595631, kelly@gamida-cell.com
|
||
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 |
27 Jun 2018
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
29 Jun 2018
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
Assess the cumulative incidence of NiCord-derived neutrophil engraftment at 42 days following transplantation.
Assess the incidence of secondary graft failure at 180 days following transplantation of NiCord.
|
||
Protection of trial subjects |
The Data Monitoring Committee met to discuss and ensure patient safety throughout the trial. The committee reviewed the accumulated data after 3 patients entered the study and were assessed at day 100 following transplant. At this initial review, the DMC monitored in particular: any occurrence of primary or secondary graft failure, as well as any substantial decrease in donor chimerism (especially myeloid chimerism), or evidence of impending graft failure, as well as all study data in general. A subsequent DMC review took place after 3 patients received the cryopreserved NiCord product and were assessed at day 100 following transplant. Early safety assessment guidelines were used to monitor primary & secondary graft failure, non-relapse mortality at 100 days and alert the DMC.
|
||
Background therapy |
1) Myeloablative conditioning regimens: (Each transplant center used the same conditioning regimen for all patients transplanted at their center). a) Regimen A (Day -11 to -2): Total Body irradiation (TBI) 1350 cGy, Fludarabine: 160 mg/m2, (optional: Cyclophosphamide: 120 mg/kg or Thiotepa: 10 mg/kg) b) Regimen B (Day -7 to -3): Thiotepa 10 mg/kg, Busulfan 9.6 mg/kg, Fludarabine 150 mg/m2 c) Regimen C (Day -5 to -2): Clofarabine 120 mg/m2, Fludarabine 40 mg/m2, Busulfan AUC 90 mg*h/L 2) GvHD prophylaxis regimen consisted of Mycophenolate Mofetil (MMF) and a calcineurin inhibitor (Tacrolimus or Cyclosporine). Each transplant center used the same calcineurin inhibitor for all patients. Tacrolimus or Cyclosporine from day -3 through day +150 Target tacrolimus trough blood levels of 5-15 ng/ml. Target cyclosporine trough levels of 200-400 ng/mL by TDX method (or 100-250 ng/mL by Tandem MS or equivalent level for other CSA testing methods). Mycophenolate Mofetil (MMF) 1 g TID IV or PO (15 mg/kg IV TID if patient weighs <50 kg) beginning day -3 to at least day +60. 3) G-CSF therapy was started on day +1 at a dose of 5 µg/kg/day continuing at least until the ANC is >1,000/µl x 2 consecutive days. | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
21 May 2013
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research | ||
Long term follow-up duration |
4 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 18
|
||
Country: Number of subjects enrolled |
Singapore: 2
|
||
Country: Number of subjects enrolled |
Italy: 1
|
||
Country: Number of subjects enrolled |
Netherlands: 3
|
||
Country: Number of subjects enrolled |
Spain: 14
|
||
Worldwide total number of subjects |
38
|
||
EEA total number of subjects |
18
|
||
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) |
3
|
||
Adults (18-64 years) |
35
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||
Recruitment
|
|||||||
Recruitment details |
Recruitment began in the US in May 2013, followed by Spain, Italy, Netherlands and Singapore. | ||||||
Pre-assignment
|
|||||||
Screening details |
59 subjects assessed for eligibility. 11 ineligible (5 progressive disease, 5 medical deterioration, 1 minimal residual disease). 5 withdrew due to projected waiting time for NiCord production. 5 transplanted with unmanipulated CBU only. 2 transplanted with unmanipulated CBU + NiCord. 36 treated with NiCord. | ||||||
Period 1
|
|||||||
Period 1 title |
Overall trial (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
|
||||||
Blinding used |
Not blinded | ||||||
Arms
|
|||||||
Arm title
|
NiCord | ||||||
Arm description |
NiCord® is a cryopreserved stem/progenitor cell based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells. NiCord® comprises: 1) cord blood-derived ex vivo expanded CD133+ cells (NiCord® cultured fraction (CF)); and 2) the non-cultured cell fraction (CD133-) of the same CBU (NiCord® Non-cultured Fraction (NF)). Both fractions, i.e. NiCord® CF and NiCord® NF, will be kept frozen until they are infused on the day of transplantation. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
NiCord
|
||||||
Investigational medicinal product code |
|||||||
Other name |
|||||||
Pharmaceutical forms |
Dispersion for infusion
|
||||||
Routes of administration |
Intravenous use
|
||||||
Dosage and administration details |
Dosage is administered once.
|
||||||
|
|
||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall trial
|
|||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Efficacy & Safety Analysis
|
|||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Any patient that received NiCord as a standalone graft.
|
|||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Additional Safety Analysis
|
|||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
included all patients who received NiCord® as a standalone, or with an unmanipulated CBU.
|
|||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
NiCord
|
||
Reporting group description |
NiCord® is a cryopreserved stem/progenitor cell based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells. NiCord® comprises: 1) cord blood-derived ex vivo expanded CD133+ cells (NiCord® cultured fraction (CF)); and 2) the non-cultured cell fraction (CD133-) of the same CBU (NiCord® Non-cultured Fraction (NF)). Both fractions, i.e. NiCord® CF and NiCord® NF, will be kept frozen until they are infused on the day of transplantation. | ||
Subject analysis set title |
Efficacy & Safety Analysis
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Any patient that received NiCord as a standalone graft.
|
||
Subject analysis set title |
Additional Safety Analysis
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
included all patients who received NiCord® as a standalone, or with an unmanipulated CBU.
|
|
|||||||||||||
End point title |
NiCord neutrophil engraftment [1] | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
42 days following transplantation
|
||||||||||||
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: This is a single-arm study; to assess the incidence of neutrophil engraftment post transplant a cumulative incidence curve will be computed along with a 95% confidence interval at 42 days post-transplant. Death prior to engraftment will be considered as a competing risk. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Secondary graft failure [2] | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
180 days
|
||||||||||||
Notes [2] - 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: This is a single-arm study; the cumulative incidence of secondary graft failure out of those who had initial engraftment will be described using the cumulative incidence estimator, treating death and disease relapse/progression prior to secondary graft failure as a competing event. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to neutrophil engraftment | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
42 days
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to platelet engraftment | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
180 days
|
||||||||||||
|
|||||||||||||
Notes [3] - Patients who engrafted neutrophils |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Platelet engraftment | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
100 days
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
non-relapse mortality | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
100 days
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Acute GVHD II-IV | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
100 days
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Acute GVHD III-IV | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
100 days
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Chronic GVHD | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
180 days
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Chronic GVHD | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
1 year
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Secondary graft failure | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
1 year
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Overall survival | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
180 days
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Overall survival | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
1 year
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
up to 1 year post-transplant
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Infections and GvHD were reported up to 1 year post-transplant.
All common events post-transplant were collected up to day 42 post-transplant. Grade 3-4 non-serious adverse events collected up to one year post-transplant.
Grade 3-5 adverse events and all grades serious adverse events have been reported to the database.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NiCord treated patients
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
20 Feb 2014 |
To expand patient population and clarify eligibility criteria |
||
20 Mar 2014 |
Change in manufacturing procedure to cryopreserved product.
Modify eligibility criteria.
Additional option for conditioning regimen. |
||
28 Aug 2014 |
Add safety objective.
Define childbearing potential and appropriate contraception. |
||
04 Dec 2014 |
Modify eligibility criteria.
Additional regimen specific stopping guidelines.
Additional supportive and viral monitoring care guidelines.
Update AE reporting guidelines. |
||
27 Mar 2015 |
Increase number of patients for study enrollment.
Modify eligibility criteria, COA release criteria, GvHD prophylaxis medication administration and assessment grading criteria. |
||
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 | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/28392378 http://www.ncbi.nlm.nih.gov/pubmed/30523748 http://www.ncbi.nlm.nih.gov/pubmed/24911148 |