CINC424A2X01B Rollover Protocol

Study Overview
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Brief Summary
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This is a long term safety study for patients that have been treated with either ruxolitinib or a combination of ruxolitinib with panobinostat, on a Novartis or Incyte sponsored study, who have been judged by the study Investigator to benefit from ongoing treatment.

Detailed Description
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This roll-over protocol allows patients from multiple protocols, who are still receiving clinical benefit, to continue their treatment in one study that covers multiple indications. The population for the roll-over study should be consistent with the population defined in the parent studies. The primary eligibility criteria for a patient to enter the roll-over protocol is the participation and completion of a Novartis or Incyte study with ruxolitinib monotherapy or combination of ruxolitinib and panobinostat. Efficacy parameters will not be measured; however safety data and an evaluation of clinical benefit will be collected.

Official Title
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Open Label, Multi-center, Phase IV Study of Ruxolitinib or Ruxolitinib and Panobinostat Combination, for Patients Who Have Completed Prior Global Novartis or Incyte Sponsored Studies

Conditions
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Thalassemia, Primary Myelofibrosis, Polycythemia Vera, Graft Versus Host Disease, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: ruxolitinib
* Drug: panobinostat


Participation Criteria
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Eligibility Criteria
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Key Inclusion criteria: Patient is currently enrolled in a Novartis GDD or GMA-sponsored or Incyte-sponsored clinical study, 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 Patient currently has no evidence of progressive disease, as determined by the investigator, following previous treatment with ruxolitinib or combination of ruxolitinib and panobinostat Key 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. Pregnant or nursing (lactating) women. 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, throughout the study and for up to 30 days after stopping study treatment. Other protocol-defined Inclusion / Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib monotherapy or ruxolitinib plus panobinostat in combination<br>All participants will receive either ruxolitinib monotherapy or ruxolitinib in combination with panobinostat, at the same dose/schedule that they were taking in the parent study. | Drug: ruxolitinib<br>* ruxolitinib tablets or pediatric oral solution - participants continue ruxolitinib as they received in parent study<br>* Other names: Jakavi;Drug: panobinostat<br>* panobinostat capsules - participants to continue receiving panobinostat in combination with ruxolitinib as per the parent study<br>* Other names: Farydak;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of AEs and SAEs | The incidence of treatment-emergent AEs and SAEs (new or worsening from baseline) will be summarized by system organ class and/or preferred term, severity (based on CTCAE grades). | 12 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with clinical benefit as assessed by the investigator at scheduled visits. | The analysis of clinical benefit will be descriptive only and cannot be compared to efficacy results of other studies. In addition, as clinical benefit was only added in protocol amendment 1, it may not be available for all participants. | 12 years | 
| Incidence and severity of AEs and SAEs by treatment group | AEs and SAEs for participants in the Safety group will be listed and summarized by treatment group (ruxolitinib monotherapy / ruxolitinib + panobinostat combination) | 12 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelofibrosis, MF, Polycythemia vera, PV, Acute Graft versus Host Disease, aGvHD, Chronic Graft versus Host Disease, cGvHD, Acute Myeloid Leukemia, AML, Thalassemia, Ruxolitinib, INC424, Panobinostat, LBH589