Clinical Trial Results:
Phase II feasibility study using ch14.18/CHO antibody and subcutaneous interleukin 2 after haploidentical stem cell transplantation in children with relapsed neuroblastoma
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Summary
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EudraCT number |
2009-015936-14 |
Trial protocol |
AT DE |
Global end of trial date |
21 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Jul 2023
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First version publication date |
07 Jul 2023
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Other versions |
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Summary report(s) |
preliminary results Adverse Events Evaluation |
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 |
CH14.18-IL2 1021
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02258815 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Hospital of Tübingen
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Sponsor organisation address |
Geissweg 3, Tübingen, Germany, 72076
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Public contact |
Prof. Dr. med. Peter Lang, Universitätsklinikum Tübingen, 49 7071290,
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Scientific contact |
Prof. Dr. med. Peter Lang, Universitätsklinikum Tübingen, 49 7071290,
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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 |
28 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Oct 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Oct 2018
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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 |
Evaluation of safety and feasibility of the chimeric 14.18 anti-GD2 monoclonal antibody (ch14.18/CHO) in combination with subcutaneous aldesleukin (IL-2, (Proleukin®)
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, 2008 and standard research practice at the Institutions, Good Clinical Practice (GCP) and applicable local regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Nov 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Austria: 16
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Country: Number of subjects enrolled |
Germany: 52
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Worldwide total number of subjects |
68
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EEA total number of subjects |
68
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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) |
5
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Children (2-11 years) |
50
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Adolescents (12-17 years) |
13
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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 |
The study population for this study included male and female patients aged less than or equal to 21 years, with relapsed neuroblastoma, who had previously received an allogeneic haploidentical SCT. | ||||||||||||
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Pre-assignment
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Screening details |
For screening, all scans including ultrasounds, CT scans, MRIs and X-rays were to be performed within two weeks prior to enrolment. CBC with platelets, human anti-chimeric antibodies and chemistries were to be done ≤ 2 weeks before study registration and meet eligibility criteria. 2 patients were excluded after the screening phase. | ||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
Due to the exploratory nature of this trial, no active control treatment was administered in parallel to a comparator group.
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Arms
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Arm title
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Treatment group | ||||||||||||
Arm description |
This was a Phase II, open-label, uncontrolled, multi-center safety and exploratory efficacy study of ch14.18/CHO mAb plus IL-2 given in a single dose group not earlier than 60 days and maximally one year after haploidentical SCT to relapsed neuroblastoma patients. Due to the exploratory nature of this trial, no active control treatment was administered in parallel to a comparator group. There was only one arm in the study | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
ch14.18/CHO
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ch14.18/CHO: 4.5 ± 0.25 mg/mL
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Investigational medicinal product name |
Interleukin-2 (IL-2)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in vial
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
1x106 IU/m2
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
68 patients, with 1st to 5th relapse, were eligible for the study. The median age at study entry was 6,5 years (range 3-20 years) with a predominance of male participants (n=46; 67,6 %). The median time from initial diagnosis to haploidentical stem cell transplantation was 33 months (range 6–171 months) All patients suffered from a stage IV relapse of a histologically confirmed neuroblastoma; most patients had also metastatic disease at initial diagnosis (94,1 %) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment group
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Reporting group description |
This was a Phase II, open-label, uncontrolled, multi-center safety and exploratory efficacy study of ch14.18/CHO mAb plus IL-2 given in a single dose group not earlier than 60 days and maximally one year after haploidentical SCT to relapsed neuroblastoma patients. Due to the exploratory nature of this trial, no active control treatment was administered in parallel to a comparator group. There was only one arm in the study | ||
Subject analysis set title |
Patients receiving full protocol treatment
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The patients who completed the full protocol treatment
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End point title |
Success of treatment [1] | ||||||
End point description |
The primary end point ‘success of treatment’ was defined as patients receiving six cycles of dinutuximab beta (DB), alive 180 days after end of trial treatment, without progression, and unacceptable toxicity or acute GvHD ≥ grade 3 or extensive chronic GvHD according to Glucksberg or Seattle classification, respectively.
Treatment success of ≥50% was considered relevant witha minimum of 35 evaluable patients for assessing efficacywith a Simon’s two-stage design (significance level 5%; power 80%), 22 followed by a validation group of 25 patients.
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End point type |
Primary
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End point timeframe |
180 days
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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: See the attached Clinical Trial Report |
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| No statistical analyses for this end point | |||||||
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End point title |
5-year Overall Survival (OS) | ||||||||
End point description |
EFS and OS were calculated from start of trial treatment (first antibody cycle in this trial, ie, first day of first dinutuximab beta (DB) cycle, after haplo-SCT).
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End point type |
Secondary
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End point timeframe |
5 years
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| No statistical analyses for this end point | |||||||||
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End point title |
5-year Event-Free Survival (EFS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
5 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Complete Remission (maintained from before) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
180 days
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Complete Remission (improved compared to before treatment) | ||||||||||||
End point description |
% of patients who experienced complete remission and meant an improvement compared to before the study treatment
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End point type |
Secondary
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End point timeframe |
180 days
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Partial Remission (PR) | ||||||||||||
End point description |
% of patients who experienced Partial Remission (PR)
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End point type |
Secondary
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End point timeframe |
180 days
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mixed response (MR), Non-remission (NR) or Progressive disease (PD) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
180 days
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
AEs were observed from the first dose of study medication within 30 days after the last study drug application or - if pre-existent - deteriorated after the first dose of study medication.
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
CTC | ||
Dictionary version |
4.0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: The safety evaluation regarding the adverse events of the trial is attached as a PDF-document. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/36854071 |
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