CINC424A2X01B Rollover Protocol

Inclusion criteria:

Patients eligible for inclusion in this study have to meet all of the following 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 rollover 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 all discussions 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.

Exclusion criteria:

Patients eligible for this study must not meet any of the following 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 until the termination of gestation, confirmed by a positive hCG laboratory test.
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 childbearing 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:

Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient.
Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.

In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.

For patients on the combination of ruxolitinib and panobinostat:

Women of childbearing potential unwilling to use highly effective methods of contraception during dosing and for 3 months (female patients of childbearing potential)
Female sexual partner(s) of childbearing potential of male participants unwilling to use highly effective methods of contraception during dosing and for 6 months after stopping.
Women of childbearing potential who use hormonal contraceptives and additionally unwilling to use a barrier method for birth control.Sexually active males (including vasectomised men) unwilling to use barrier contraception (condom with spermicide) during intercourse and for 6 months after stopping treatment (in order to prevent delivery of the drug via seminal fluid).