Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary MF (POMINC)

Inclusion Criteria:

• Age ≥18 years at the time of voluntarily signing an IRB/IEC-approved informed consent
• Diagnosis of Myeloproliferative Neoplasms (MPN) either de novo myelofibrosis according to WHO criteria (PMF), secondary myelofibrosis (post-PV MF and post-ET MF) according to the IWG-MRT consensus terminology)
• Anemia with hemoglobin level of <10 g/dl or transfusion-dependent anemia
• Splenomegaly (>11 cm total diameter) and/or leukoerythroblastosis
• Adequate organ function, i.e. ALT and/or AST <3 x upper limit of normal (ULN), total bilirubin <3 x ULN, and serum creatinine <2 mg/dl
• Subject must be willing to receive transfusion of blood products
• ECOG performance status <3
• Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.*
• Reliable contraception should be maintained throughout the study and for 28 days after study treatment discontinuation
• Unless practicing complete abstinence from heterosexual intercourse, sexually active FCPB must agree to use adequate contraceptive methods
• Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP. Males must agree not to donate semen or sperm

• All subjects must:

  1. understand that the investigational product could have a potential teratogenic risk.
  2. be counseled about pregnancy precautions and risks of fetal exposure.
  3. agree to abstain from donating blood while taking investigational. agree not to share study medication with another person and to return all unused study drug to the investigator.

Exclusion Criteria:

• Pregnant or breast feeding females
• BCR/ABL-positivity
• Diagnosis of ET (according to WHO 2008 criteria)

• Diagnosis of PV (according to WHO 2008 criteria)

  ->20% blasts in peripheral blood or bone marrow

• thrombocytopenia <100 /nl or transfusion-dependent thrombocytopenia
• neutropenia <0.5 /nl
• Known positive status for HIV, HBV or HCV
• Prior treatment with IMiDs (thalidomide, lenalidomide) or with Interferon-alpha within a 3 month time period before Screening-phase
• History of thrombosis or pulmonary embolism within 6 months prior to study entry
• Peripheral neuropathy >grade 1 CTC
• 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.
• Presence of any medical/psychiatric condition or laboratory abnormalities which may limit full compliance with the study, increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study
• Drug or alcohol abuse within the last 6 months
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.
• Patients undergoing treatment with hematopoietic growth factor receptor agonists (i.e., erythropoietin [Epo], granulocyte colony stimulating factor (GCSF [Neupogen; Neulasta], romiplostim, eltrombopag) within a 4 weeks period prior to screening-phase.
• Patients receiving any medication listed in the Appendix IV "Prohibited Medications" (within 7 days prior to the first dose of study drug).
• Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
• Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 28 days of screening.