This is a phase I/II protocol investigating whether Nelfinavir can improve anemia and lower serum fibrosis biomarkers in Myelofibrosis patients.

Inclusion Criteria:

• ≥18 years of age
• Have a diagnosis of myelofibrosis (MF) according to the 2016 WHO criteria
• Has a hemoglobin ≤ 10gm/dL at screening
• Serum ferritin ≥ 100
• May continue on current MPN treatment, including aspirin, hydroxyurea, interferon-alpha, ruxolitinib, fedratinib, or anagrelide.
• Peripheral blast count <10% during Screening.
• Free of other known active or metastatic malignancies other than localized skin cancer.
• Amenable to blood draws and symptom assessments.
• Agree to the use of contraceptives. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential, should both use an effective contraception method during the study and continue to use contraception for 60 days after the last dose of study drug.

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) questionnaire score of ≥3

• Currently pregnant or planning on being pregnant within the study period.

• Currently taking Momelotinib or Pacritinib (these agents are purported to reduce hepcidin).

• Currently taking any of the contraindicated medications to Nelfinavir listed in section 13.2

• Currently breastfeeding.

• Known uncontrolled active viral or bacterial infection.

• Known HIV+

• Significant impairment of major organ or hematopoietic function defined as

  1. Serum creatinine clearance less than 30 ml/min (eGFR).
  2. Bilirubin more than 1.5 mg/dl except for Gilbert's disease. ALT or AST more than 2X upper normal limit or has radiologic evidence of liver cirrhosis.
  3. Platelets < 50 × 10^9/L without transfusions
  4. ANC < 0.75 × 10^9/L without growth factors

• Known history of allergic reaction to nelfinavir.