Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
Condition: Venous Thromboembolism; Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thromboembolism; Venous Thromboembolism
Intervention: Apixaban
Intervention description: apixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months
Intervention MeSH terms: Apixaban
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: venous thromboembolism; multiple myeloma; anticoagulation

Summary:

      Patients living with multiple myeloma (MM) have an increased risk of venous thromboembolism
      (VTE) due to the disease itself and the use of targeted therapies, including immunomodulatory
      drugs (IMiDs). Prevention of VTE has become a major management challenge during MM treatment.
      There is a paucity of data with respect to the non-vitamin K oral anticoagulants (NOACs) in
      the cancer population. However, the NOACs offer comparable efficacy but improved safety
      compared with warfarin. Apixaban has shown excellent safety and efficacy for treatment and
      prevention of recurrent VTE (1,2). The safety and efficacy of apixaban for primary prevention
      of VTE in MM patients has not been established.

      Aim #1: To quantify the 6-month rate of major and clinically relevant non-major bleeding in
      MM patients receiving IMiDs who are prescribed apixaban 2.5 mg orally twice daily for primary
      prevention of VTE.

      Hypothesis #1: The 6-month rate of major and clinically relevant non-major bleeding in MM
      patients receiving IMiDs who are prescribed apixaban 2.5 mg orally twice daily for primary
      prevention of VTE will be ≤3% (2). Although the MM population, in general, has a higher
      medical acuity than that of the previous large randomized controlled trials of apixaban, we
      will be selecting a stable population of MM patients who are appropriate for immunomodulatory
      therapy.

      Aim #2: To quantify 6-month rate of symptomatic VTE in MM patients receiving IMiDs who are
      prescribed apixaban 2.5 mg orally twice daily for primary prevention of VTE.

      Hypothesis #2: The 6-month rate of symptomatic VTE in MM patients receiving IMiDs who are
      prescribed apixaban 2.5 mg orally twice daily for primary prevention of VTE will be <7% (3).
      Although additional therapies for MM such as dexamethasone and erythropoietin-stimulating
      agents may further increase the risk of VTE, the rate of incident VTE should be reduced to
      <7% with apixaban.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women

          -  Age > 18 years

          -  Current or prior diagnosis of symptomatic MM based on International Myeloma Working
             Group (IMWG) guidelines (http://imwg.myeloma.org/category/guidelines-2/) and will be
             starting or already receiving IMiD therapy with thalidomide [Thalomid], lenalinomide
             [Revlimid], or pomalidomide [Pomalyst]

          -  IMiD therapy given in the setting of newly diagnosed MM, relapsed MM, progressive MM,
             maintenance therapy or consolidation therapy as per IMWG criteria

          -  Willing to provide written informed consent

          -  Eastern Cooperative Oncology Group (ECOG) functional status ≤ 2

          -  Providers must plan to treat the patient with IMiD therapy for a minimum of 6 cycles

        Exclusion Criteria:

          -  Pregnancy

          -  Breastfeeding

          -  Women of child-bearing potential who are unwilling or unable to use an acceptable
             method of birth control (such as oral contraceptives, other hormonal contraceptives
             [vaginal products, skin patches, or implanted or injectable products], or mechanical
             products such as an intrauterine device or barrier methods [diaphragm, condoms,
             spermicides]) to avoid pregnancy for the entire study

          -  Any prior venous thromboembolism

          -  Contraindication to anticoagulant therapy

          -  Conditions for which serious bleeding may occur including:

               1. Current or within last 6 months: intracranial bleeding, intraocular bleeding,
                  gastrointestinal bleeding, endoscopically documented ulcer disease

               2. Current or within last month: head trauma or other major trauma, major surgery

               3. Current or within last 2 weeks: stroke, neurosurgical procedure

               4. Current: gross hematuria, major unhealed wound, major surgery planned during the
                  trial period, intracranial mass, vascular malformation, or aneurysm, overt
                  bleeding, blood dyscrasia

               5. CNS involvement of MM or other history of CNS malignancy

          -  Active and clinically significant liver disease

          -  Uncontrolled hypertension: systolic blood pressure >180 mm Hg or diastolic blood
             pressure >100 mm Hg

          -  Current endocarditis

          -  Requirement for ongoing anticoagulant therapy, including mechanical heart valve
             replacement and atrial fibrillation

          -  Severe valvular heart disease, including rheumatic heart disease and mitral stenosis

          -  Bioprosthetic heart valve replacement

          -  Requirement for dual antiplatelet therapy or single agent antiplatelet therapy with
             clopidogrel, prasugrel, or ticagrelor

          -  Requirement for aspirin at a dose higher than 165 mg daily.

          -  Hemoglobin < 9 mg/dL at time of screening

          -  Platelet count < 100,000/mm3 at time of screening

          -  Serum calculated creatinine clearance (CrCl) < 25 ml/m at time of screening

          -  Alanine aminotransferase or aspartate aminotransferase level > 2 times the upper limit
             of the normal at time of screening

          -  Total bilirubin level > 1.5 times the upper limit of the normal at time of screening

          -  Life expectancy < 12 months or hospice care

          -  Prisoners or subjects who are involuntarily incarcerated

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness

          -  Receiving concurrent non-FDA-approved or investigational agents or has received an
             investigational agent within the past 30 days prior to the first dose of study
             treatment (with the exception of approved medications being used for an approved
             indication, e.g., investigating a new dosing regimen for an approved indication).

          -  Any condition, which in the opinion of the investigator, would put the subject at an
             unacceptable risk from participating in the study

          -  Any other medical, social, logistical, or psychological reason, which in the opinion
             of the investigator, would preclude compliance with, or successful completion of, the
             study protocol