Clinical Trial Results:
Phase 2 Clinical Trial with Ponatinib as a Second Line Therapy for Patients with Chronic Myeloid Leukemia in Chronic Phase Resistant or Intolerant to prior First Line Tyrosine Kinase Inhibitor Treatment
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Summary
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EudraCT number |
2016-000618-30 |
Trial protocol |
DE |
Global end of trial date |
22 Jun 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Jun 2024
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First version publication date |
27 Jun 2024
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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 |
11272
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03807479 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GWT-TUD GmbH
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Sponsor organisation address |
Freiberger Str. 33, Dresden, Germany, 01067
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Public contact |
Fachbereich MEDIZIN, GWT-TUD GmbH, +49 35125933100, medical.consulting@g-wt.de
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Scientific contact |
Fachbereich MEDIZIN, GWT-TUD GmbH, +49 35125933100, medical.consulting@g-wt.de
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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 |
18 Dec 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Jun 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Jun 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Major molecular response (MMR) by 12 months of treatment with second line Ponatinib treatment
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Protection of trial subjects |
The conduct of this study was in compliance with the Good Clinical Practice Guidelines and under the guiding principles detailed in the Declaration of Helsinki. The study was also carried out in keeping with applicable local law(s) and regulation(s).
Patients who are treated within ponatinib may encounter ocular damage. Therefore, prior to study start, an ophthalmologist needs to confirm patients’ suitability for the study. During the course of the trial, patients need to be asked for any changes on visual acuity. In case a change is observed, an ophthalmologist again needs to be consulted in order to confirm that patient is safe to continue on the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2018
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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 |
Germany: 18
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Worldwide total number of subjects |
18
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EEA total number of subjects |
18
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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) |
16
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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 |
From 12 Dec 2018 until 25 Jan 2022, in total 22 patients were screened at 6 study sites in Germany. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
18 received study medication and were included in the evaluation. Eleven patients were enrolled after failure and seven after intolerance to 1st line TKI treatment. | ||||||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Treatment period | ||||||||||||||||||||
Arm description |
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Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Ponatinib
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Investigational medicinal product code |
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Other name |
Iclusig
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Starting dose of 30 mg (2 tablets à 15 mg) once daily. Doses might have been increased in case of inappropriate response or reduced to manage drug-related adverse events with re-escalation once events resolved.
If a patient had reached a major molecular response (MMR), the dose reduction to 15 mg/day could have been considered. Patients remained on study until disease progression or unacceptable toxicity occurred.
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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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End points reporting groups
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Reporting group title |
Treatment period
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Reporting group description |
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End point title |
major molecular response (MMR) [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 months
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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: A maximum of 54 patients was planned to be treated. Based on historical data, the rate of MMR by 12 months in the 2nd line setting is approximately 0.3. The goal of therapy was to improve this to at least 0.5. With one-sided α-error rate of 0.025 and power of 0.8, z-test for binominal proportion with continuity adjustment was used. |
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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 |
12 months
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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 |
23.0
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Reporting groups
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Reporting group title |
Overall
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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02 Sep 2021 |
Protocol Version 4.0: Specification of inclusion/exclusion criteria, reduction of frequency of bone marrow and viral Hep B analysis, recruitment time extended from 30 to 42 months |
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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. | |||
| Due to the low recruitment rate, the study was terminated prematurely after inclusion of 22 patients. | |||
