Apixaban in Thrombocytopenia

Inclusion Criteria:

• Active malignancy defined as histologically confirmed diagnosis within last 6 monthsor received any cancer directed therapy within the last 6 months.

• Radiologically confirmed newly diagnosed symptomatic deep vein thrombosis orpulmonary embolism within 28 days of enrollment. Includes proximal lower-limb DVT orsymptomatic PE. Upper extremity or catheter-associated thrombosis will be included,as will distal lower extremity DVTs.

• Platelet count < 75,000/ml (prior to platelet transfusion) within 28 days of VTEdiagnosis.

• Platelet count responsive to transfusion if previously administered (defined as anaverage platelet increase of at least 10,000/ml over the last 3 transfusions.

• No evidence of active hemorrhage.

• No recent history of major hemorrhage (requiring transfusion, hospitalization orintervention) within the last 12 months.

• No known brain metastases.

• Age ≥18 years. Because no dosing or adverse event data are currently available onthe use of apixaban in participants <18 years of age, children are excluded fromthis study, but will be eligible for future pediatric trials.

• ECOG performance status ≤2

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

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

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

• Glomerular filtration rate (GFR) ≥25 mL/min/1.73/m2

• Human immunodeficiency virus (HIV)-infected participants on effectiveanti-retroviral therapy with undetectable viral load within 6 months are eligiblefor this trial.

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

• Participants with a history of hepatitis C virus (HCV) infection must have beentreated and cured. For participants with HCV infection who are currently ontreatment, they are eligible if they have an undetectable HCV viral load.

• The effects of apixaban on the developing human fetus are unknown. For this reason,women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry andfor the duration of study participation. Should a woman become pregnant or suspectshe is pregnant while she or her partner is participating in this study, she shouldinform her treating physician immediately. Men treated or enrolled on this protocolmust also agree to use adequate contraception prior to the study, for the durationof study participation, and 4 months after completion of apixaban administration.

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

Exclusion Criteria:

• Participants who are receiving any other investigational agents.

• Participants who have had a thrombectomy, insertion of a caval filter, or require afibrinolytic agent.

• Participants that have index events with severe clot burden defined as bilateralproximal lower extremity deep vein thrombosis and saddle embolism or pulmonaryembolism with hemodynamic compromise.

• Participants with acute myeloid leukemia or myelodysplastic syndrome or who areundergoing or have undergone allogeneic stem cell transplant.

• Participants with luminal gastrointestinal malignancy or genitourinary cancer.

• Presence of known or prior brain metastasis, given the increased risk oflife-threatening intracranial hemorrhage with anticoagulant use. While screening forbrain metastases is not standard of care in this population, investigators mayobtain brain imaging if clinically indicated prior to initiation of anticoagulation.Imaging is not mandated in order to participate in this study.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to apixaban.

• Participants receiving any medications or substances that are inhibitors or inducersof CYP3A/P-gp 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 on aspirin (>100 mg/day), dual antiplatelet therapy, or receivingchronic treatment with NSAIDS

• Participants with uncontrolled intercurrent illness.

• Participants at high risk of bleeding such as:

• Unresected luminal/mucosal GI and GU cancers

• Active gastric or duodenal cancer

• History of major bleeding (based on ISTH criteria) in the past 12 months

• Any prior history of Intracranial hemorrhage (microhemorrhage is not included)

• Clinical or laboratory concern for ongoing DIC (prolonged PT/APTT or lowfibrinogen)

• Severe renal disease (CKD Stage IV or higher) or liver disease (Child Pugh B/C)

• Participants with pre-planned major surgery within the study period

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

• Pregnant women are excluded from this study because apixaban has the potential forteratogenic or abortifacient effects. Because there is an unknown but potential riskfor adverse events in nursing infants secondary to treatment of the mother withapixaban, breastfeeding should be discontinued if the mother is treated withapixaban.

• Participant must be able to swallow pills.