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

This is an interventional treatment trial for Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase focused on measuring Myelofibrosis Transformation in Essential Thrombocythemia Read More

Inclusion Criteria:

• 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 resistant to, intolerant of, or ineligible for Janus kinase (JAK)2 inhibitor therapy, or have refused such therapy
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
• Absolute neutrophil count >= 1.0 x 10^9/L
• Platelets >= 75 x 10^9/L
• Total bilirubin =< institutional upper limit of normal (ULN) (or =< 3 X ULN if Gilbert's syndrome present or if bilirubin increase related to MF)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) =< 2.5 X institutional ULN
• Creatinine clearance >= 50 mL/min/1.73 m^2 (calculated by estimated glomerular filtration rate [eGFR] from EPIC)
• Female subjects who are pregnant or breast-feeding are not eligible; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; likewise, should a female partner of a male patient become pregnant or suspect she is pregnant while participating in the study, he should inform his treating physician and the female partner should call her physician immediately

• Female of child bearing potential (FOCBP) must have a negative pregnancy test (serum or urine) within 7 days prior to registration on study; NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria:

• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis; etc.) within the past 3 years prior to the start of treatment

  • The following are exceptions to this criterion: subjects with vitiligo or alopecia; subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; or subjects with psoriasis not requiring systemic treatment
• Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
• Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab; the following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (eg. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10 mg/day of prednisone or equivalent; (NOTE: If systemic corticosteroids are part of the treatment regimen for the indication under study, the systemic corticosteroid is permitted)
• Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control from starting dose of durvalumab (cycle 1 day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab are not eligible; female subjects should agree to refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab
• Male subjects who are not employing an effective method of birth control from starting dose of durvalumab (cycle 1 day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab are not eligible; male subjects should agree to refrain from sperm donation while taking durvalumab and for at least 90 days after the last dose of durvalumab; should a female partner of a male patient become pregnant or suspect she is pregnant while participating in the study, he should inform his treating physician and the female partner should call her physician immediately
• History of hypersensitivity to durvalumab or any excipient
• Receipt of live attenuated vaccination within 30 days prior the first dose of durvalumab
• Patients may not be receiving any other investigational agents within 2 weeks prior to registration
• Patients who have had prior exposure to checkpoint blockade therapy, such as anti-PD-1/PD-L1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-CD137, and anti-OX40 antibody therapy, are not eligible

• Patients who have an inter-current illness including, but not limited to any of the following, are not eligible:

  • Severe hypertension that is not controlled on medication (>= 140/90 mmHg for 3 consecutive readings)
  • Ongoing or active infection requiring systemic treatment
  • Congestive heart failure with New York Heart Association (NYHA) classification of 3
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with another malignancy, unless they have been disease free for 3 years prior to registration (with the exception of squamous cell carcinoma or basal cell carcinoma of the skin or cervical intraepithelial neoplasia)
  • 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
• Unwilling or unable to comply with the protocol