Clinical Trial Results:
An open-label, multicenter study of INC424 monotherapy or in combination with azacitidine for patients with post-myeloproliferative disorders (MPD) – AML or with CMML
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Summary
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EudraCT number |
2014-000346-30 |
Trial protocol |
DE |
Global end of trial date |
28 Nov 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Sep 2021
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First version publication date |
23 Sep 2021
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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 |
CINC424XDE04T
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
University of Leipzig
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Sponsor organisation address |
Ritterstrasse 26, Leipzig, Germany, D 04109
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Public contact |
Studiensekretariat Hämatologie, Universität Leipzig, 0049 34197 13 130,
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Scientific contact |
Studiensekretariat Hämatologie, Universität Leipzig, 0049 34197 13 130,
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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 Nov 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Feb 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Nov 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 |
Phase I: Feasibility to administer INC424 alone or in combination with azacitidine on 4 patients.
Phase II: To collect efficacy data on AML secondary to MPN and on CMML either with INC424 alone or in combination with azacitidine.
This phase did not start because phase I was not successful.
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Protection of trial subjects |
prophylactic use of fluoroquinolone and
oral antifungal during neutropenia is recommended,
broad-spectrum antibiotic if neutropenic fever occurs;
if fever persists despite the use of antibiotic, myeloid growth factor is applied at the descretion of the investigator.
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Background therapy |
Standard administration of hydroxyurea | ||
Evidence for comparator |
low evidence for treatment of newly diagnosed AML with azacitidine, no evidence for combination treatment with azacitidine and ANC2424 of patients with post-myeloproliferative disorders. | ||
Actual start date of recruitment |
03 Nov 2014
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Long term follow-up planned |
No
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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 |
Germany: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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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) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
3
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
FPI on January 15, 2015; last patient in on March 27, 2017 | ||||||||||||
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Pre-assignment
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Screening details |
Four patients with secondary AML and one patient with CMML were enrolled | ||||||||||||
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Period 1
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Period 1 title |
Phase I (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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Jakvida | ||||||||||||
Arm description |
INC 424 in monotherapy or in combination with azacitidine | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Jakavi
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Investigational medicinal product code |
Ruxolitinib
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Other name |
ANC 424
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
following the therapy scheme (Trial Protocol, figure 1)
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Investigational medicinal product name |
Vidaza
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Investigational medicinal product code |
Azacitidine
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
following the therapy scheme (Fig. 1 of the Trial Protocol)
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Baseline characteristics reporting groups
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Reporting group title |
Phase I
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Reporting group description |
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End points reporting groups
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Reporting group title |
Jakvida
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Reporting group description |
INC 424 in monotherapy or in combination with azacitidine | ||
Subject analysis set title |
FAS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full analysis set
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End point title |
Haematological response [1] | ||||||||||||||||||||||||
End point description |
Response following the IWG response criteria for AML / myelofibrosis
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End point type |
Primary
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End point timeframe |
84 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: This is a single arm study. Confirmatory statistics is not applicable. |
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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 |
Screening, baseline
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Adverse event reporting additional description |
Toxicities are recorded after each treatment period
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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 |
20.1
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Reporting groups
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Reporting group title |
Jakvida
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Reporting group description |
Treatment arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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27 Mar 2017 |
Substantial changes:
- The deputy of the coordinating investigator, one member of the DMC and the project manager at the ZKS Leipzig - KKS changed.
- Description of the trial design was changed.
- Due to prolonged patient recruitment, the expected trial duration is adapted. |
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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. | |||
| The study was terminated because of insufficient patient accrual. The trial ended unscheduled in phase I with only 5 patients with incomplete courses. Efficacy evaluation was not possible. | |||
