Siltuximab in Treating Patients With Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis

• Patients must have a histologically confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (post-PV) myelofibrosis (MF), or post-essential thrombocythemia (post-ET) MF using World Health Organization Criteria
• Patients must have disease that requires therapy, including intermediate-1, intermediate-2, or high-risk disease according to the International Prognostic Scoring System (IPSS) or Dynamic-IPSS
• Patients must be off myeloproliferative neoplasm (MPN) directed therapy, such as Janus kinase (JAK)-inhibitors, for at least 2 weeks prior to administration of the study drug; NOTE: This does not include supportive transfusion, or hydroxyurea; these must be stopped prior to first day of treatment, but no wash -out period is required
• Patients must be resistant to, intolerant of, or ineligible for JAK2 inhibitor therapy, based on severe anemia or thrombocytopenia
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• New York Heart Association functional classification for congestive heart failure (NYHA CHF) \< 3
• Patients must have clinical laboratory values meeting the following criteria within 28 days prior to registration:
• Absolute neutrophil count >= 1.0 x 10\^9/L (without growth factor support)
• Platelet count >= 20 x 10\^9/L (without transfusion support within 2 weeks of registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN)
• Alkaline phosphatase =\< 2.5 x ULN
• Total bilirubin =\< 2.5 x upper limit of normal (ULN) except if the elevation is due to Gilbert's syndrome (allowable at =\< 5 x ULN) or myelofibrosis (per principle investigator [PI] discretion)
• Calculated creatinine clearance > 20 mL/min per institutional standard

• Before enrollment, a woman must be one of the following:

  • Not of childbearing potential, defined as:

    • Postmenopausal (> 45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level > 40 IU/mL)
    • Permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy)
    • Otherwise be incapable of pregnancy
  • Of childbearing potential and practicing a highly effective method of birth control (consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies) during the study and for 3 months after receiving the last dose of study agent NOTE: Examples include established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidals (including foam/gel/film/cream/suppository) or occlusive cap (diaphragm or cervical/vault caps) with spermicidals; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject); Note: If the childbearing potential changes after start of the study (e.g., woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above
• Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to registration
• Female patients must agree (during the study and for 3 months after receiving the last dose of study agent, not to donate eggs (ova, oocytes) for the purposes of assisted reproduction
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidals or partner with occlusive cap with spermicidals and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
• Patients must be willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

• Patients with prior exposure to agents targeting interleukin 6 (IL -6) or the IL-6 receptor are not eligible

• Patients with another malignancy, unless they have been disease free for 2 years prior to registration, with the exception of

  • Basal cell or non-metastatic squamous cell carcinoma of the skin
  • Cervical carcinoma in situ or International Federation of Gynecology and Obstetrics (FIGO) stage 1 carcinoma of the cervix

• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:

  • Ongoing or active infection requiring concurrent systemic antibiotic treatment: there is no mandatory duration of time that a patient has to be off antibiotics, but the treating physician has to deem the infection as effectively treated prior to enrollment
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Patients who have received vaccination with live attenuated vaccines within 6 months prior to registration are not eligible
• Patients who are on any prohibited medication; they have to be have a wash-out period of at least 2 weeks prior to registration, in order to be eligible for the study
• Patients with clinically significant infection, including known human immunodeficiency virus (HIV), human herpesvirus-8 (HHV-8), hepatitis C infection, or known hepatitis B surface antigen positivity are not eligible
• Female patients who are pregnant or breast-feeding are not eligible; NOTE: A woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study agent should likewise not be considered for this study
• Patients who have received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 14 days or 5 half -lives before registration or is currently enrolled in the treatment stage of an investigational study are not eligible; please contact PI for further details on wash-out period and eligibility of such patients
• Patients who have been hospitalized for infection or major surgery (e.g., requiring general anesthesia) within 2 weeks before registration or have not fully recovered from surgery are not eligible; Note: Subjects with surgical procedures conducted under local anesthesia may participate
• Patients who are unwilling or unable to comply with the protocol