Clinical Trial Results:
JeRiCHO (JAK-inhibition in recurrent classical Hodgkin Lymphoma): A phase II, open-label, prospective, non-randomized, multicenter clinical trial with the JAK-inhibitor ruxolitinib in patients with relapsed or refractory Hodgkin Lymphoma (HL).
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Summary
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EudraCT number |
2013-003369-33 |
Trial protocol |
DE |
Global end of trial date |
30 Jun 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Jun 2020
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First version publication date |
25 Jun 2020
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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 |
Uni-Koeln-1698
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02164500 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Cologne
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Sponsor organisation address |
Albertus Magnus-Platz, Köln, Germany, 50923
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Public contact |
Trial Coordination Center of the German Hodgkin Study Group (GHSG), German Hodgkin Study Group (GHSG), 0049 22147888200, ghsg@uk-koeln.de
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Scientific contact |
Trial Coordination Center of the German Hodgkin Study Group (GHSG), German Hodgkin Study Group (GHSG), 0049 22147888200, ghsg@uk-koeln.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 |
20 Mar 2020
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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 |
30 Jun 2019
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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 |
To determine the objective response rate (complete response + partial response) of ruxolitinib in patients with relapsed or refractory classical Hodgkin lymphoma
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Protection of trial subjects |
Written informed consent prior to study entry; 2-stage design with comprehensive interim risk-benefit assessment and formal futility criterion after stage 1; standardized dose reduction in case of adverse events
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Oct 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
12 Months | ||
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: 14
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Worldwide total number of subjects |
14
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EEA total number of subjects |
14
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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) |
8
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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 |
Recruitment for stage 1 was open between 28 Oct 2015 and 12 May 2017. It was planned to enroll 12 response-eligible patients in stage 1. We enrolled 14 patients, of whom 2 were not eligible for primary endpoint analysis. The trial was terminated after stage-1 analysis. No patients were enrolled in stage 2. | ||||||||||||
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Pre-assignment
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Screening details |
Main inclusion criteria: Relapsed or refractory histologically confirmed cHL that is progressing or active and requires treatment after ≥ 1 appropriate therapy including ASCT if eligible; Age ≥ 18 years; ECOG ≤ 2; adequate organ function. Main exclusion criteria: Relevant concurrent disease; pregnancy or lactation. | ||||||||||||
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Period 1
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Period 1 title |
Stage 1 (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 |
Continuous 28-day cycles of ruxolitinib until disease progression, withdrawal of consent or intolerable toxicity | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Ruxolitinib
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Investigational medicinal product code |
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Other name |
Jakavi (R)
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ruxolitinib was applied twice a day (approximately 12 hours apart: morning and night) with a starting dose of 25 mg per application. Ruxolitinib dose was to be decreased (5 mg bid steps) per standardized dosing paradigm in case of adverse events. Ruxolitinib tablets were administered orally without regards to food in an outpatient setting. The dosage strength was 5 mg/tablet ruxolitinib (free base equivalent). Ruxolitinib was dispensed on day 1 of each cycle by the study center personnel. Patients were provided with an adequate supply of ruxolitinib for self-administration at home.
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Baseline characteristics reporting groups
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Reporting group title |
Stage 1
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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 |
Continuous 28-day cycles of ruxolitinib until disease progression, withdrawal of consent or intolerable toxicity | ||
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End point title |
Objective response rate (ORR) after 2 cycles by central review [1] | ||||||||||
End point description |
Objective response was defined as complete or partial remission in the centrally reviewed PET/CT-based restaging after 2 cycles of ruxolitinib. The primary endpoint was to be analyzed per-protocol, excluding patients who received less than 2 cycles ruxolitinib unless due to progressive disease.
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End point type |
Primary
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End point timeframe |
PET/CT-based restaging was to be performed at day 26-30 of the second cycle (last day of cycle +/- 2 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: According to the trial protocol, the null hyothesis H0: ORR ≤ 5% was to be tested in a 2-stage design. The trial was terminated after stage 1 although the required responders were observed (1 responder required, 2 responders observed). Thus, only descriptive analyses of the primary endpoint in the stage-1 per-protocol population were done. |
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| Notes [2] - Per-protocol analysis excluding 2 patients due to disconfirmation of cHL diagnosis |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Best response | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From the restaging after two cycles onwards, restagings with a modality at the investigator’s discretion (local standard of care) were to be performed every three months until end of study treatment.
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End point title |
Progression-free survival | ||||||||
End point description |
Progression-free survival was analyzed according to Kaplan-Meier.
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End point type |
Secondary
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End point timeframe |
Progression-free survival was calculated for each patient as time between the date of completion of staging and the date of first progression, relapse or death or, in cases of continuing response, the date of the last documented follow-up.
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Adverse events information
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Timeframe for reporting adverse events |
AEs were assessed from start of study treatment up until the 28-day follow-up visit or the start of a new HL therapy, whichever occurred first.
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Adverse event reporting additional description |
Expected AEs of CTCAE grades 3/4 were assessed on the therapy administration CRFs by predefined CTCAE categories. Unexpected and serious AEs were assessed on specific forms and coded according to MedDRA.
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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 |
10.2
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Reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Patients received continuous 28-day cycles of oral ruxolitinib, with 25 mg bid (approximately 12 hours apart: morning and night) as starting dose. Ruxolitinib dose was to be decreased (5 mg bid steps) per standardized dosing paradigm in case of adverse events. Treatment was continued until disease progression, withdrawal of consent or intolerable toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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18 Jan 2016 |
Updated ICF, implementation of regulatory authority and ethics committee authorizations |
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19 Sep 2016 |
Amendment of dose reduction section due to changes in SmPC of ruxolitinib |
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22 Feb 2018 |
Amendment of the frequency of side effects due to changes in SmPC of ruxolitinib |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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 trial was terminated after stage 1 due to slow recruitment and low response rates/PFS in line with protocol guidance although required responders were observed (1 required, 2 observed). Only descriptive analysis in stage-1 population were done. | |||||||
