Clinical Trial Results:
A Phase II study of oral JAK1/JAK2 inhibitor INC424 in adult patients with relapsed/refractory classical Hodgkin’s lymphoma
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Summary
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EudraCT number |
2012-004246-15 |
Trial protocol |
BE |
Global end of trial date |
12 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Sep 2018
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First version publication date |
22 Sep 2018
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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 |
HIJAK
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01877005 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
LYSARC
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Sponsor organisation address |
Centre Hospitalier LYon Sud - secteur Sainte Eugénie - Pavillon 6D, Pierre Bénite, France, 69495
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Public contact |
Elise Gaire, Clinical Project Manager, LYSARC, 33 472669333, elise.gaire@lysarc.org
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Scientific contact |
Pr Franck Morschhauser
Co-coordinating Investigator, LYSA, 33 320444290, ranck.morschhauser@chru-lille.fr
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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 |
30 Jul 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Jun 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 |
To assess the efficacy of oral JAK1/2 inhibitor ruxolitinib measured by overall response rate (ORR) by IWG criteria (Cheson 2007) occurring after 6 months of oral JAK1/2 inhibitor ruxolitinib treatment in patients with advanced HL for whom no treatment with proven efficacy is available
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Protection of trial subjects |
Patients have been followed for safety (adverse event) during all study duration.
If a patient does not respond to study treatment, relapses or has progressive disease, each site was free
to initiate further treatment according to local guidelines
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
01 Jul 2013
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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 |
Belgium: 7
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Country: Number of subjects enrolled |
France: 26
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Worldwide total number of subjects |
33
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EEA total number of subjects |
33
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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) |
27
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
1st patient was included on 10/07/2013 and last patient on 16/12/2014. 33 patients were included | ||||||||||||||||||
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Pre-assignment
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Screening details |
No patient created in eCRF was screen failed | ||||||||||||||||||
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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 | ||||||||||||||||||
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Arms
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Arm title
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Experimental | ||||||||||||||||||
Arm description |
Induction period: oral ruxolitinib will be given twice daily during 6 cycles of 28 days Maintenance period: patients who achieve at least a SD (according Cheson 2007) at the end of cycle 6 and for whose a clinical benefit is observed according to the Investigator’s opinion will be eligible for maintenance treatment by ruxolitinib (15mg or 20mg) twice daily every day of 28-day cycles. Treatment should be continued up to 2 years or until disease progression, intolerability and/or the investigator determine that further therapy is not in the patient’s best interest (e.g., due to non-compliance, toxicity, etc.) Dose regimen: 20 mg BID of ruxolitinib if platelets > 200 x 109/L 15 mg BID of ruxolitinib if platelets count is between 75 to 200 x 109/L (+ dose escalation allowed) | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Ruxolitinib
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Investigational medicinal product code |
INC424
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The induction treatment consists of 6 cycles of 28 days with ruxolitinib administrated every day continuously at the following dosage:
- Subjects with baseline platelet count > 200 x 109/L will begin dosing at 20 mg BID
- Subjects with baseline platelet count between 75 and 200 x 109/L will begin dosing at 15mg BID
Patients who achieve at least a SD (according Cheson 2007) at the end of cycle 6 and for whose a clinical benefit is observed according to the Investigator’s opinion will be eligible for maintenance treatment by ruxolitinib (at the same posology for the induction period) twice daily every day of 28-day cycles. Treatment should be continued up to 2 years or until disease progression, intolerability and/or the
investigator determine that further therapy is not in the patient’s best interest (e.g., due to noncompliance, toxicity etc.)
Ruxolitinib tablets will be administered orally twice daily (BID) approximately 12 hours apart, without regards to food.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Induction period: oral ruxolitinib will be given twice daily during 6 cycles of 28 days Maintenance period: patients who achieve at least a SD (according Cheson 2007) at the end of cycle 6 and for whose a clinical benefit is observed according to the Investigator’s opinion will be eligible for maintenance treatment by ruxolitinib (15mg or 20mg) twice daily every day of 28-day cycles. Treatment should be continued up to 2 years or until disease progression, intolerability and/or the investigator determine that further therapy is not in the patient’s best interest (e.g., due to non-compliance, toxicity, etc.) Dose regimen: 20 mg BID of ruxolitinib if platelets > 200 x 109/L 15 mg BID of ruxolitinib if platelets count is between 75 to 200 x 109/L (+ dose escalation allowed) | ||
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End point title |
Overall response at the end of treatment after 6 cycles of ruxolitinib during induction phase [1] | ||||||||
End point description |
Overall response rate (CR+ PR) according to the Criteria for evaluation of response in Non-Hodgkin’s
lymphoma (Cheson, 2007).
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End point type |
Primary
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End point timeframe |
At the end of treatment after 6 cycles of ruxolitinib during induction phase.
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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: No statistical analysis is performed for the primary endpoint of the study as the overall response rate is only a percent calculation. |
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| Notes [2] - Evaluable set: includes all enrolled patients who have received at least 28 days of study medication |
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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 |
Adverse events were reported from the date of informed consent signature to 30 days after last drug administration.
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Adverse event reporting additional description |
Due to the expected toxicity of study treatment, were reported in eCRF:
- grade ≥ 3 toxicities
- grade ≥ 2 for infections
- toxicities of any intensity of grade related to a Serious Adverse Event
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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 |
4
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Reporting groups
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Reporting group title |
Safety set
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Reporting group description |
The safety set includes all patients who have received at least one dose of study medication | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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26 Aug 2013 |
• The addition in the biochemical analysis of the blood of two additional biological parameters (C-reactive protein and β2-microglobulin) and replacement of a parameter (measurement of the acid uric in place of urea), being essential for the assessment of patients before and during treatment
• The addition of a recommendation to perform a lymph node biopsy to relapse before inclusion in the protocol
• Clarification of concomitant treatments prohibited (reported inconsistency after the first set up): the authorization to take systemic steroids at a dose ≤ 20mg (as prednisolone equivalent) in Annex 9 and page 21
• A precision made on the realization of the tumoral evaluation visits for a better understanding: in Cycle 6 (end of induction) the evaluation should be carried out within 7 days before the end of induction to decide if the patient is responder to the treatment and continues the maintenance.
• Same precision for maintenance cycles
• A precision made on the time of realization of the samples for the biological study on biomarkers (page 25 and Appendix 8)
• Update of the start and end dates of the study (page 3 and synopsis)
• Modification of "Flow Chart" of the study: correction of an inconsistency and the addition of evaluation visits during maintenance period. |
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10 Jan 2014 |
• Expansion of the maintenance phase to patients with stable disease and in which a clinical benefit is observed at the end of induction,
• Modification of the study design (page 41 of the protocol) accordingly |
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25 Jul 2014 |
• Modification of ruxolitinib packaging (from bottles of 60 tablets to wallets of 56 tablets) |
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28 May 2015 |
• Addition of an anatomopathological study on biopsy samples already collected |
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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. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/29351986 |
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