E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This roll-over study is designed to accept patients with varied disease origins. Please refer to the parent protocol for the disease background information and rationale for use of ruxolitinib in their individual indications. |
Cette étude de poursuite de traitement est conçue pour inclure des patients aux pathologies diverses. Veuillez consulter le protocole pour les détails concernant ces pathologies et les raisons d’un traitement avec le ruxolitinib dans chaque indication. |
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E.1.1.1 | Medical condition in easily understood language |
This study is designed to accept patients with varied disease origins. Please refer to the parent protocol. |
Cette étude est conçue pour inclure des patients aux pathologies diverses. Veuillez consulter le protocole d’étude. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10074689 |
E.1.2 | Term | Post polycythemia vera myelofibrosis |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10074690 |
E.1.2 | Term | Post essential thrombocythemia myelofibrosis |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10074691 |
E.1.2 | Term | Post polycythaemia vera myelofibrosis |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10074692 |
E.1.2 | Term | Post essential thrombocythaemia myelofibrosis |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054658 |
E.1.2 | Term | Thalassemia |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066264 |
E.1.2 | Term | Acute graft versus host disease in intestine |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066262 |
E.1.2 | Term | Acute graft versus host disease in skin |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066263 |
E.1.2 | Term | Acute graft versus host disease in liver |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066260 |
E.1.2 | Term | Acute graft versus host disease |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066261 |
E.1.2 | Term | Chronic graft versus host disease |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072160 |
E.1.2 | Term | Chronic graft versus host disease in liver |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072158 |
E.1.2 | Term | Chronic graft versus host disease in intestine |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072159 |
E.1.2 | Term | Chronic graft versus host disease in skin |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate long term safety data i.e. SAEs and AEs. |
Evaluer les données de sécurité d’emploi à long terme, c’est-à-dire les EI et les EIG. |
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E.2.2 | Secondary objectives of the trial |
To evaluate clinical benefit as assessed by the investigator
Other secondary:
- To evaluate long term safety data by ruxolitinib in monotherapy or in combination with
panobinostat
- To evaluate clinical benefit by ruxolitinib in monotherapy or in combination with panobinostat |
Evaluer le bénéfice clinique selon le jugement de l'investigateur.
Autres objectifs secondaires:
- Evaluer les données de sécurité d’emploi à long terme du ruxolitinib en monothérapie ou en association avec le panobinostat
- Evaluer le bénéfice clinique du ruxolitinib en monothérapie ou en association avec le panobinostat
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient is currently enrolled in a Novartis GDD or GMA-sponsored or Incyte-sponsored clinical study (where Incyte can delegate the sponsorship to a preferred CRO, if applicable) that is approved to enroll into this rollover study, and are receiving either ruxolitinib or combination of ruxolitinib and panobinostat, and fulfilled all of the requirements of the parent protocol..
- Patient is currently benefiting from the treatment with ruxolitinib monotherapy or combination of ruxolitinib and panobinostat, as determined by the investigator
- Patient has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements
- Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures
- Patient currently has no evidence of progressive disease, as determined by the investigator, following previous treatment with ruxolitinib or combination of ruxolitinib and panobinostat
- Written informed consent obtained prior to enrolling in roll-over study and receiving study medication. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
Note 1: If the patient is a minor, the parent who signs the informed consent for the minor
must be a legally recognized parent or guardian. Where deemed appropriate by the clinician, and the child’s parent or guardian, the child will also be included in the alldiscussions about the trials and the minor aged 12 and above assent will be obtained. The parent or guardian will sign on the designated line on the ICF attesting to the fact that the child had given consent.
Note 2: if the minor is an adolescent female, she will be informed during the assent process that for safety purpose, a pregnancy test is required. She will also be told that if it is positive, she will be counseled and will be assisted in telling her parents. If the minor does not want to proceed, she will be advised not to sign consent and her enrollment in this protocol will end. |
- Le patient est actuellemen inclus dans une étude clinique promue par Novartis GDD ou Novartis GMA ou Incyte (Incyte pouvant déléguer le parrainage à une CRO choisie, le cas échéant) et autorisé à participer dans cette étude de poursuite du traitement, et être sous traitement par ruxolitinib ou l’association de ruxolitinib et de panobinostat et avoir satisfait à toutes les exigences du protocole parent.
- Le patient bénéficies du traitement actuel par ruxolitinib en monothérapie ou en association avec le panobinostat, selon l’évaluation de l'investigateur.
- Observance par le patient des exigences du protocole de l'étude parente, selon jugement de l'investigateur
- Volonté et capacité à respecter les visites programmées, les plans de traitement et toutes les autres procédures de l'étude.
- Absence de tout signe de progression, tel que déterminé par l'investigateur, à la suite d'un traitement antérieur par ruxolitinib ou l’association de ruxolitinib et de panobinostat.
- Recueil du consentement éclairé écrit avant le recrutement dans l'étude de poursuite du traitement et être sous médicament de l’étude. Si le consentement ne peut être exprimé par écrit, il doit être recueilli de manière formelle et devant témoin(s), idéalement par un témoin de confiance et indépendant.
Remarque 1 : Si le patient est mineur, le parent qui signe le consentement éclairé du mineur doit être un parent ou un titulaire de l'autorité parentale légalement reconnu. Lorsque le clinicien et le parent de l’enfant ou le titulaire de l'autorité parentale le jugent utile, l’enfant sera également associé à toutes les discussions relatives aux essais et le consentement des mineurs âgés de 12 ans et plus sera recueilli. Le parent ou le titulaire de l'autorité parentale apposera sa signature sur la ligne du formulaire de consentement éclairé (ICF) prévue à cet effet pour attester que l'enfant a donné son consentement.
Remarque 2 : si l’enfant mineur est une adolescente, elle sera informée au cours de la procédure de consentement que, pour des raisons de sécurité, un test de grossesse est nécessaire. Il lui sera dit également que si le résultat est positif, elle sera conseillée et assistée pour informer ses parents. Si la mineure ne veut plus participer à l'étude, il lui sera conseillé de ne pas signer son consentement, et son recrutement pour ce protocole prendra fin. |
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E.4 | Principal exclusion criteria |
- Patient has been permanently discontinued from study treatment in the parent study due to any reason.
- Patient’s indication is currently approved and reimbursed in the local country
- Patient has participated in a combination trial other than the panobinostat and ruxolitinib
combination trial (CLBH589X2106), where ruxolitinib was dispensed in combination with another study medication and the patient is still receiving combination therapy.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- Female patients between ≥ 12 and < 18 years of age and of childbearing potential (e.g. are
menstruating) who do not agree to abstinence or, if sexually active, do not agree to the use of highly effective contraception as defined below, throughout the study and for up to 30 days after stopping treatment
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study duration inclusive of the 30-day safety follow up. Highly effective contraception methods include: see protocol.
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- Arrêt définitif du traitement dans l'étude parente, quelle qu'en soit la cause.
- L’indication pour laquelle le patient prend le traitement est actuellement approuvée et remboursée dans son pays.
- Participation antérieure à un essai d'association thérapeutique autre que l’essai sur l'association de panobinostat et de ruxolitinib (CLBH589X2106), dans lequel le ruxolitinib était administré en association avec un autre médicament à l’étude et jusqu’à la fin de la grossesse, confirmée par un dosage biologique positif d'hCG.
- Grossesse ou allaitement au sein, la grossesse étant définie comme l'état de la femme après la conception et jusqu'au terme de la gestation, confirmée par un dosage biologique positif d'hCG.
- Patientes âgées entre12 ans et 17 ans en âge de procréer (par ex, ayant eu leurs premières règles) qui refusent de respecter une abstinence totale de toute activité sexuelle ou d'utiliser, si elles sont sexuellement actives, une méthode de contraception telle que définie ci-dessous, tout au long de l’étude et pendant 30 jours après l'arrêt du traitement.
Femmes en âge de procréer, à savoir toute femme physiologiquement apte à être enceinte, sauf si elles utilisent des méthodes de contraception très efficaces pendant toute la durée de l’étude y compris pendant le suivi de la sécurité de 30 jours. Les méthodes de contraception très efficaces sont: voir protocole.
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E.5 End points |
E.5.1 | Primary end point(s) |
Frequency and severity of SAEs/AEs
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Fréquence et sévérité des EI/EIG |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
through study completion estimated to be approximately 10 years |
jusqu'à la fin de l'étude d’une durée prévisionnelle de 10 ans |
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E.5.2 | Secondary end point(s) |
Proportion of patients with clinical benefit as assessed by the investigator at scheduled visits
Other secondary:
- frequency and severity of AEs/SAEs
- Proportion of patients with clinical benefit as assessed by the investigator at scheduled visits |
Proportion de patients présentant un bénéfice clinique d'après l’évaluation de l'investigateur lors des visites programmées.
Autres secondaires:
- fréquence et sévérité des EI/EIG
- Proportion de patients présentant un bénéfice clinique d'après l’évaluation de l'investigateur lors des visites programmées
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at every visit that occur every 12 weeks until EOT
other secondary:
- at every visit that occur every 12 weeks until End of Trial
- at every visit that occur every 12 weeks until End of Trial |
à chaque visite qui a lieu toutes les 12 semaines jusqu'à la fin du traitement
autres secondaires :
- à chaque visite qui a lieu toutes les 12 semaines jusqu'à la fin du traitement
- à chaque visite qui a lieu toutes les 12 semaines jusqu'à la fin du traitement
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To better characterize the long term safety of ruxolitinib in patients from existing global Novartis or Incyte sponsored studies who are benefiting from treatment after conclusion of the parent study |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 86 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Bulgaria |
Chile |
China |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Lebanon |
Mexico |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Saudi Arabia |
South Africa |
Spain |
Sweden |
Thailand |
Turkey |
United Kingdom |
Jordan |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study will occur after all patients in the study have completed their last assessment per protocol. Patients may continue on study treatment until one of the following criteria is met, whichever comes first:
• End of Treatment
• At least one of the premature patient withdrawal criteria are met
• 10 years after the first patient’s first visit into this clinical study
• Current treatment becomes commercially available and reimbursed in that indication |
La fin de l'étude aura lieu une fois que tous les patients auront terminé leur dernière évaluation selon le protocole.
Les patients peuvent poursuivre le traitement jusqu'à ce que l'un des critères suivants soit satisfait selon la première de ces éventualités
Fin du traitement
Au moins un des critères de retrait prématuré du patient est rempli
10 ans à compter de la première visite du premier patient
jusqu’à ce que le traitement soit commercialisé et remboursé dans l’indication respective |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 12 |