An Extension Study for Patients Previously Enrolled in Studies With Pelabresib

Inclusion Criteria:

* Able to provide signed informed consent, agreeing to all protocol and ICF requirements.
* At least 18 years old and legally able to consent in the study's jurisdiction.
* Previously enrolled and currently receiving pelabresib in combination with ruxolitinib or ruxolitinib alone in a parent study.
* Demonstrating clinical benefit from pelabresib and/or ruxolitinib, as judged by the investigator.
* Willing and able to follow all study visits, treatments, and procedures.
* Agree to avoid pregnancy or fathering children:

  * Men: Must use highly effective contraception (≥99% effective) and avoid sperm donation from eligibility check through 94 days post-treatment.
  * Women of childbearing potential (WOCBP): Must test negative for pregnancy at eligibility, use highly effective contraception through 184 days post-treatment, undergo regular pregnancy testing, and avoid breastfeeding and oocyte donation during this period.
  * Women not of childbearing potential (surgically sterile or postmenopausal ≥12 months without other cause) are eligible.

Note: Women with amenorrhea due to chemo/radiotherapy are considered WOCBP and must use contraception.

Additional Inclusion Criteria control (placebo + ruxolitinib) group requiring pelabresib combination treatment:

* On a stable dose of ruxolitinib for ≥8 weeks
* Has adequate bone marrow and organ function as defined by the following local laboratory values:

  * ANC ≥ 1 × 10\^9/L in the absence of growth factors for the previous 4 weeks
  * Platelet count ≥ 75 × 10\^9/L in the absence of growth factors or platelet transfusions during previous 4 weeks
  * Peripheral blood blast count \< 5%
  * AST and/or ALT ≤ 2.5 × ULN of the local reference interval (≤ 5 × if the elevation can be ascribed to hepatic MF involvement, e.g., presence of hepatomegaly)
  * Serum direct bilirubin \< 2.0 × ULN of the local reference interval
  * Calculated or measured CrCl of ≥ 45 mL/min
* Does not have any other concurrent medical condition that in the opinion of the investigator could compromise participation in the study

Exclusion Criteria:

* Legally institutionalized or under judicial protection.
* Enrolled in another interventional clinical trial (excluding the parent study).
* History of hypersensitivity to pelabresib, its excipients, or similar drugs.
* Significant gastrointestinal issues (e.g., active IBD, unresolved nausea/vomiting/diarrhea \> Grade 1) that may affect drug absorption.
* Any medical condition deemed unsuitable by the investigator.
* Uncontrolled illness or condition that may compromise safety or protocol compliance.
* Received systemic anticancer or investigational treatment (excluding parent study drug or hormonal therapy) within 2 weeks or 5 half-lives before first dose. (Hydroxyurea/anagrelide allowed up to 24 hours prior.)
* Received hematopoietic growth factors or androgenic steroids within 4 weeks before first dose.
* Used strong CYP3A4 inhibitors/inducers (e.g., St. John's wort) within 2 weeks before first dose. Use during treatment is prohibited.
* Received immunosuppressive agents with systemic activity (\>10 mg QD prednisone or equivalent) less than 4 weeks before the first dose of study drug in the extension study. Participants who received topical, nasal, intra-articular, inhaled, and other forms of corticosteroids without systemic activity are eligible
* Received a live vaccination within 30 days prior to the first dose of study drug in the extension study, except for COVID-19 vaccination
* Female participants who are pregnant, breastfeeding, or not using required contraception.
* Male participants who do not agree to use contraception or refrain from sperm donation as specified.
* Unwilling or unable to comply with the study protocol.

Additional Exclusion Criterion for participants receiving ruxolitinib only treatment

• Local access to commercially available and reimbursed ruxolitinib.