A study for patients who have completed a prior global Novartis or Incyte sponsored ruxolitinib (INC424) study or a study of ruxolitinib in combination panobinostat (LBH589) or siremadlin (HDM201) orrineterkib (LTT462) and are judged by the investigator to benefit from continued treatment

Phase 1

• Conditions: 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.; MedDRA version: 21.0Level: LLTClassification code 10074689Term: Post polycythemia vera myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10074690Term: Post essential thrombocythemia myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10074691Term: Post polycythaemia vera myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10074692Term: Post essential thrombocythaemia myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10036061Term: Polycythemia veraSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: LLTClassification code 10054658Term: ThalassemiaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 27.0Level: PTClassification code 10066264Term: Acute graft versus host disease in intestineSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 27.0Level: PTClassification code 10066262Term: Acute graft versus host disease in skinSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.1Level: PTClassification code 10066263Term: Acute graft versus host disease in liverSystem Organ Class: 10021428 - Immune system disorders

• Registration Number: EUCTR2014-003527-22-SE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-18
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 366

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 38
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 196
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate long term safety data i.e. SAEs and AEs.;Secondary Objective: To evaluate clinical benefit as assessed by the investigator<br>Other secondary:<br>- To evaluate long term safety data by ruxolitinib in monotherapy or in<br>combination with<br>panobinostat or siremadlin (HDM201) or rineterkib (LTT462)<br>- To evaluate clinical benefit by ruxolitinib in monotherapy or in combination with panobinostat or siremadlin (HDM201) or rineterkib<br>(LTT462);Primary end point(s): Frequency and severity of SAEs/AEs<br>;Timepoint(s) of evaluation of this end point: through study completion estimated to be approximately 10 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Proportion of patients with clinical benefit as assessed by the<br>investigator at scheduled visits<br>Other secondary:<br>- frequency and severity of AEs/SAEs<br>- Proportion of patients with clinical benefit as assessed by the<br>investigator at scheduled visits;Timepoint(s) of evaluation of this end point: at every visit that occur every 12 weeks until EOT<br>other secondary:<br>- at every visit that occur every 12 weeks until End of Trial<br>- at every visit that occur every 12 weeks until End of Trial