Ruxolitinib in Thrombocythemia and Polycythemia Vera

Inclusion Criteria:

• Patients who have been diagnosed with essential thrombocythemia or polycythemia veraby World Health Organization 2016 diagnostic criteria.

• Patients with essential thrombocythemia must be very low (no history of thrombosis,age <60, and no JAK2 mutation), low (no history of thrombosis, age <60, presence ofJAK2 mutation), or intermediate risk (no history of thrombosis, age >60, no JAK2mutation) by IPSET criteria. Patients with polycythemia vera must be low risk (nohistory of thrombosis and age <60) by NCCN guidelines.

• Patients with an MPN-SAF TSS (MPN-10) score >10 AND at least one individual feature >5 documented on a separate visit within 3 months prior to study registration, asdocumented in the clinical record or obtained by clinician. If not previouslydocumented in the electronic medical record, participants must be blinded to purposeof MPN SAF TSS scoring for eligibility determination. Average daily MPN-SAF TSS (MPN-10) score must remain >10 with any individual feature >5 for the week-longbaseline assessment prior to ruxolitinib initiation.

• Patients who have previously received or are receiving cytoreductive therapy (i.e.hydroxyurea, anagrelide, interferon) are eligible for the study if therapy was usedfor the indication of symptom control, or if therapy was used for pre-operativecontrol of blood counts. If a subject is still receiving cytoreductive therapy atthe time of screening and enrollment, there will be a wash-out period from priorcytoreductive therapy at least 7 days prior to ruxolitinib initiation.

• Age ≥18 years.

• ECOG performance status ≤2 (Karnofsky ≥60%)

• Participants must have adequate organ and marrow function as defined below:

• leukocytes ≥3,000/mcL

• absolute neutrophil count ≥1,500/mcL

• platelets ≥100,000/mcL

• total bilirubin ≤ institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

• creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥60mL/min/1.73 m2 unless data exists supporting safe use at lower kidney functionvalues, no lower than 30 mL/min/1.73 m2

• Participants with a prior or concurrent malignancy not receiving treatment forconcurrent cancer diagnosis and/or prior concurrent malignancy within 5 years exceptfor basal cell carcinoma or squamous cell carcinoma of the skin.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated.

• For participants with evidence of chronic human immunodeficiency virus (HIV)infection, they must be negative for HBV DNA, HCV RNA, or hepatitis B surfaceantigen (BsAg) on suppressive therapy, if indicated.

• Participants must be previously vaccinated with the Herpes Zoster (Shingles) vaccineor must be willing to start prophylactic Acyclovir 400 mg twice daily (BID) orsuitable alternative for duration of treatment with ruxolitinib.

• Participants with known history or current symptoms of cardiac disease, or historyof treatment with cardiotoxic agents, should have a clinical risk assessment ofcardiac function using the New York Heart Association Functional Classification. Tobe eligible for this trial, participants should be class 2B or better.

• Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

• Essential thrombocythemia patients who are high risk by IPSET-R criteria (age > 60with JAK2 V617F mutation and/or history of thrombosis).1 Polycythemia vera patientswho are high risk by NCCN guidelines (age > 60 and/or history of thrombosis).

• Patients with >5% blasts on baseline marrow exam or at any other time in peripheralblood

• Participants who are receiving any other investigational agents.

• Participants with a history of splenectomy. Participants may still be eligible afterdiscussion with and approval by the Overall PI, however.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to ruxolitinib or excipients of ruxolitinib.

• Participants requiring any medications or substances that are strong inhibitors or 3A4 isozyme are ineligible. Because the lists of these agents are constantlychanging, it is important to regularly consult a frequently-updated medicalreference. As part of the enrollment/informed consent procedures, the participantwill be counseled on the risk of interactions with other agents, and what to do ifnew medications need to be prescribed or if the participant is considering a newover-the-counter medicine or herbal product.

• Participants with uncontrolled intercurrent illness.

• Participants with inadequate liver or renal function at screening as evidenced bylab values not meeting criteria

• Participants with psychiatric illness/social situations that would limit compliancewith study requirements.

• Pregnant women are excluded from this study because ruxolitinib is a Class C agentwith the potential for teratogenic or abortifacient effects. Because there is anunknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with ruxolitinib, breastfeeding should be discontinued ifthe mother is treated with ruxolitinib.

• The effects of ruxolitinib on the developing human fetus are unknown. Pregnant womenand subjects of childbearing potential who are unwilling to take appropriateprecautions to avoid becoming pregnant or fathering a child are ineligible. Women ofchild-bearing potential and men must agree to use adequate contraception (hormonalor barrier method of birth control; abstinence) prior to study entry and for theduration of study participation. Should a woman become pregnant or suspect she ispregnant while she or her partner is participating in this study, she should informher treating physician immediately. Men treated or enrolled on this protocol mustalso agree to use adequate contraception prior to the study, for the duration ofstudy participation, and 4 months after completion of ruxolitinib administration.