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

PRIMARY OBJECTIVES:

I. To determine the efficacy/clinical activity of nivolumab in patients with myelofibrosis
(MF).

SECONDARY OBJECTIVES:

I. To determine the safety of nivolumab in patients with MF.

TERTIARY OBJECTIVES:

I. To explore time to response and duration of response. II. To assess changes in symptom
burden. III. To explore changes in bone marrow fibrosis. IV. To explore changes in Janus
kinase 2 valine at amino acid position 617 (JAK2V617F) (or other molecular marker) allele
burden or changes in cytogenetic abnormalities.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 60 minutes once every 2 weeks for 8 doses
and then once every 12 weeks thereafter. Treatment may continue for up to 4 years in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, and 100 days.

Inclusion Criteria:

- Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera)
requiring therapy, including those previously treated and relapsed or refractory, or
if newly diagnosed, with intermediate-1 or -2 or high risk according to International
Prognostic Scoring System (IPSS)

- Previously treated with ruxolitinib (unless not a good candidate for ruxolitinib
therapy in the judgment of treating physician)

- Palpable splenomegaly or hepatomegaly of more than or equal to 5 cm below left or
right, respectively, costal margin on physical exam

- Understanding and voluntary signing an institutional review board (IRB)-approved
informed consent form

- No prior history of immune checkpoint modulator therapy

- Disease-free of other malignancies

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

- Negative pregnancy test in females of childbearing potential (FCBP); male patients
with female partners of child-bearing potential and female patients of childbearing
potential are required to use two forms of acceptable contraception, including one
barrier method, during their participation in the study and for 23 weeks (for females)
or 31 weeks (for males) following the last dose of study medication; acceptable forms
of contraception include 1 highly effective method such as an intrauterine device
(IUD), hormonal (birth control pills, injections, or implants), tubal ligation, or
partner's vasectomy and at least 1 additional approved barrier method such as a latex
condom, diaphragm, or cervical cap plus spermicide; female patients of childbearing
potential must not be breast-feeding or planning to breast feed and must have a
negative pregnancy test within 24 hours of the first study treatment

- Direct bilirubin equal to or less than 1.5 x upper limit of normal (ULN)

- Serum creatinine equal to or less than 1.5 x ULN

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) equal to
or less than 2.5 x ULN (unless considered to be related to MF or patient has known
history of Gilberts, in which case it must be equal to or less than 5 x ULN)

Exclusion Criteria:

- Use of any other standard or experimental therapy within 14 days of starting study
therapy

- Lack of recovery from all toxicity from previous therapy to grade 1 or baseline

- Any concurrent severe and/or uncontrolled medical conditions that could increase the
patient's risk for toxicity while in the study or that could confound discrimination
between disease- and study treatment-related toxicities

- Documented history of a cerebral vascular event (stroke or transient ischemic attack),
unstable angina, myocardial infarction, or cardiac symptoms consistent with New York
Heart Association class III-IV within 6 months prior to their first dose of the study
drugs

- Patients who are currently receiving chronic (> 14 days) treatment with
corticosteroids at a dose equal to or more than 10 mg of prednisone (or its
glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment
that cannot be discontinued prior to starting study drug

- Patients with autoimmune diseases are excluded: patients with a history of
inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are
excluded from this study as are patients with a history of autoimmune disease (e.g.,
rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus
erythematosus, autoimmune vasculitis)

- Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state
of a female after conception and until the termination of gestation, confirmed by a
positive beta-human chorionic gonadotropin (HCG) laboratory test

- Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A,
B or C

- The use of dietary supplements or herbal medications within 7 days of starting study
therapy