Fedratinib in Combination With Nivolumab

Exclusion Criteria

• •1. Planned hematopoietic stem cell transplantation within 3 months and suitable donor available
• •2. \>10% blasts in bone marrow smear (cytology) or \>2x in blood smear within the screening phase or \>20% blasts at any time in bone marrow or peripheral blood smears
• •3. Creatinine \>2xULN and Creatinine-Clearance \<45ml/min; ALAT, ASAT \& bilirubin \>3xULN (if MF impact on liver \>5xULN)
• •4. Baseline platelets count below 50 x 10\^9/L and ANC \< 1.0 x 10\^9/L
• •5. Diagnosis of PV, ET (according to WHO 2016) or positive molecular test for BCR-ABL
• •6. Patients on ongoing medication for myelofibrosis including systemic corticosteroids (detailed list of permitted medications is provided in paragraph 9.1.10.4 and Appendix V). Use of steroids within 14 days prior to the first dose of study drug and until end of treatment is prohibited by patients.
• •7. Uncontrolled infection
• •8. Evidence of acute or chronic infection with hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or tuberculosis
• •9. Current participation in any other interventional clinical study within 30 days before the first administration of the investigational product or at any time during the study, unless it is an observational (non-interventional) study, or during the follow-up period of an interventional study with last dose of investigational product ≥30 days prior first administration of investigational product within this study.
• •10. No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician about study participation
• •11. No consent for biobanking of patient's biological specimens
• •12. Prior therapy with checkpoint-inhibitors
• •13. Vaccination within 4 weeks prior to treatment start
• •14. Hypersensitivity to the IMPs or to any of the excipients
• •15. History of or uncontrolled autoimmune disease such as autoimmune-hepatitis, -pneumonitis, -thyroiditis, chronic inflammatory bowel disease, multiple sclerosis, or rheumatologic diseases (including but not limited to systemic lupus and vasculitis)
• •16. History of malignancy except for i) adequately treated local basal cell or squamous cell carcinoma of the skin, ii) asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, or iii) any other cancer that has been in complete remission for ≥ 5 years
• •17. Secondary malignancy that limits survival to less than 6 months.
• •18. Drug or alcohol abuse within the last 6 months
• •19. Patients who cannot adhere to the Pregnancy Prevention Plan
• •20. Pregnant or breast-feeding females
• •21. Thiamine levels below normal limit despite supplementation
• •22. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts \[§ 40 Abs. 1 S. 3 Nr. 3a AMG\]