A Pilot Study Investigating Apixaban and Dexamethasone InterAction in Multiple Myeloma
Condition: Anti-Xa Activity
MeSH terms: Multiple Myeloma
Intervention: apixaban
Intervention description: 2.5 mg PO BID
Intervention MeSH terms: Apixaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This pilot study will investigate the impact of dexamethasone (DEX) on anti-Xa levels in
      participants taking apixaban 2.5 mg twice a day by mouth (PO BID). Investigators propose a
      prospective, cohort study of 24 participants with multiple myeloma, in whom a
      lenalidomide-dexamethasone (LEN-DEX)-based myeloma treatment regimen is indicated. Eligible
      participants will initiate thromboprophylaxis with apixaban prior to starting their
      DEX-containing regimen and continue until the end of cycle 3. Anti-Xa levels, D-Dimer and
      plasma drug concentration will be measured.

      This pilot study looks to investigate this potential interaction between apixaban and
      dexamethasone to see if it warrants further investigation in a larger study.

      The sample size of 24 provides 90% power to detect a primary outcome of ≥ 50% reduction in
      peak anti-Xa levels from baseline. Secondary outcomes include changes in plasma apixaban
      levels, D-dimer, and symptomatic venous thromboembolism (VTE) and bleeding during a 3-month
      treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with diagnosis of multiple myeloma according to criteria of the International
             Myeloma Working Group

          -  Patients in whom a LEN-DEX-based treatment regimen is indicated

          -  Adult patients ≥ 19 years of age who are able to freely provide informed consent

        Exclusion Criteria:

          -  Concomitant antiplatelet or anticoagulant use

          -  Calculated creatinine clearance < 30 mL/min by Cockcroft-Gault formula

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times upper
             limit of normal (ULN)

          -  Total bilirubin > 2 x ULN

          -  Thrombocytopenia < 50 x 10 gigalitres (Gl)

          -  High bleeding risk or spontaneously prolonged prothrombin time or activated partial
             thromboplastin time > 1.5 x ULN

          -  Body weight <50 or >120 kg

          -  Concomitant use of CYP3A4 or p-glycoprotein inducers or inhibitors

          -  Use of Ginkgo biloba or St. John's Wort within 14 days before first dose of study drug

          -  Dexamethasone use within last 3 months

          -  Women of Childbearing potential without proper contraceptive measures, pregnancy or
             breast feeding

          -  Life expectancy less than 3 months

          -  Inability to swallow or issues with malabsorption

          -  Any other medical, social, logistical, geographical or psychological factors, which in
             the opinion of the investigator, would prohibit follow-up, compliance and study
             completion