| 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. |
|
| 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. |
|
| 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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10010331 - Congenital, familial and genetic disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 27.0 |
| 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 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 27.0 |
| 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 |
|
| 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 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 27.0 |
| 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 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 27.0 |
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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. |
|
| 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 or siremadlin (HDM201) or rineterkib (LTT462)
- To evaluate clinical benefit by ruxolitinib in monotherapy or in combination with panobinostat or siremadlin (HDM201) or rineterkib (LTT462) |
|
| 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, or combinations of
ruxolitinib and siremadlin (HDM201), or ruxolitinib and rineterkib
(LTT462), and fulfilled all of the requirements of the parent protocol.
Please refer to the list of parent studies in Appendix 2.
- Patient is currently benefiting from the treatment with ruxolitinib
monotherapy or combination of ruxolitinib and panobinostat, or
combinations of ruxolitinib and siremadlin (HDM201), or ruxolitinib and
rineterkib (LTT462), 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, or
combinations of ruxolitinib and siremadlin (HDM201), or ruxolitinib and
rineterkib (LTT462)
- 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. |
|
| 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
corresponding country for ruxolitinib monotherapy or combination of
ruxolitinib and panobinostat (if the patient is receiving combination
treatment in the parent study)
- 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 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 study treatment. If local regulations
are more stringent than the contraception methods listed in the protocol
and in Section 7.1.7 to prevent pregnancy, the local regulations will
apply as described in the ICF. Highly effective contraception methods include:
see protocol.
- Patient has participated in a combination study other than the
CINC424H12201 platform study providing combinations of either
ruxolitinib and siremadlin or ruxolitinib and rineterkib, where ruxolitinib
was dispensed in combination with another study medication
- Sexually active males, unless they use a condom during intercourse
while taking siremadlin or rineterkib and for 2 weeks after siremadlin or
rineterkib discontinuation, and thus do not attempt to father a child in
this period. A condom is required to be used also by vasectomized men
in order to prevent delivery of the drug via seminal fluid.
- Had history of documented severe hypersensitivity
reactions/immunogenicity to a prior biologic product in any treatment
arm OR received a monoclonal antibody or immunoglobulin-based agent:
• For treatment arms with rineterkib or siremadlin arms within ≤4
weeks of screening or ≤5 half-lives whichever is shorter for rineterkib or
siremadlin arms
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Frequency and severity of SAEs/AEs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| through study completion estimated to be approximately 10 years |
|
| 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 |
|
| 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 |
|
| 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
|
|
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 83 |
| 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 |
| Argentina |
| Chile |
| Switzerland |
| Taiwan |
| Australia |
| Brazil |
| Canada |
| China |
| India |
| Israel |
| Japan |
| Jordan |
| Korea, Republic of |
| Lebanon |
| Mexico |
| Russian Federation |
| Saudi Arabia |
| South Africa |
| Thailand |
| Belgium |
| Bulgaria |
| Czechia |
| Denmark |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Lithuania |
| Norway |
| Poland |
| Portugal |
| Romania |
| Slovakia |
| Slovenia |
| Spain |
| Sweden |
| Türkiye |
|
| 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
|
End of the study will occur after all pts 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
•12 yrs after the 1st patient's 1st visit into this clinical study
•Current treatment becomes commercially available and reimbursed in
that indication
•PSDS becomes available in other programs |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 12 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 12 |
| 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 |
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