Inclusion Criteria:

• Must voluntarily sign an ICF and must be able to meet all study requirements.
• For escalation, subjects must have a pathologically confirmed diagnosis of PPV-MF, PETMF, or PMF as per the EHA or WHO diagnostic criteria (note that all diagnoses must include the presence of at least Grade 1 marrow fibrosis according to the European Consensus on Grading of BM Fibrosis as well as int-1, int-2, or high risk disease according to the IWG-MRT Dynamic IPSS; Patients with PV may enter the trial if they meet the labeled indication for ruxolitinib (e.g., hydroxyurea resistant or refractory):
  • Escalation Stage 1 patients: who have not achieved normalization of splenomegaly, symptomology, or blood counts with at least 8 weeks therapy with a steady dose of ruxolitinib;
  • Escalation Stage 2: patients who have not yet received therapy with any JAK-STAT inhibitory agents or patients on at least 8 weeks of a steady dose of ruxolitinib; patients with exposure to other JAK-STAT inhibitory agents are not eligible. After discussion with the study chair or designee, patients with suboptimal response on at least 8 weeks of a steady dose of ruxolitinib may be allowed to de-escalate ruxolitinib therapy in order to enter a safety cohort which is enrolling patients at a lower dose; patients must receive the lower dose of ruxolitinib for at least 7 consecutive days without event before adding TGR-1202. If the patient completed screening evaluations including bone marrow biopsy/aspirate prior to ruxolitinib de-escalation, it need not be repeated after de-escalation provided that all evaluations occurred within 28 days prior to the first dose of TGR-1202.
• For expansion, subjects may have a pathologically confirmed diagnosis of MF or PV as noted above. There are also two expansion cohorts for patients with MDS/MPN (CMML, aCML, RARS-T or MDS/MPN-U) which warrants treatment. Patients with these diagnoses may be eligible, provided they are able to obtain ruxolitinib from commercial supply; patients who have not yet received therapy with any JAK-STAT inhibitory agents or patients on at least 8 weeks of a steady dose of ruxolitinib; patients with exposure to other JAK-STAT inhibitory agents are not eligible.
• A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score, and consent is required prior to that bone marrow biopsy to assure tissue is collected for protocol mandated testing.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Life expectancy of at least six months.
• Additional Inclusion Criteria may apply.

Exclusion Criteria:

• Other invasive malignancies within the last 2 years, except non-melanoma skin cancer and localized cured prostate, cervical cancer, and DCIS.
• History of cerebral vascular accident, unstable angina, myocardial infarction, or ventricular arrhythmia within the last 6 months.
• Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the subject properly providing informed consent or any condition which would jeopardize compliance with the protocol.
• Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection (hepatitis B carriers with normal LFTs and undetectable viral loads are allowed).
• Organ transplant recipients other than bone marrow transplant.
• Women who are pregnant or lactating.
• Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneic stem cell transplant within 6 months. Grade II, or greater, active graft versus-host disease.
• Additional Exclusion Criteria may apply.