Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma

The intended study is designed as a a phase IV pragmatic multicenter randomized controlled clinical trial, comparing the impact of two different therapies including ASA vs. Rivaroxaban in newly diagnosed or relapsed and refractory multiple myeloma patients treated with Lenalidomide Dexamethasone (Len-Dex) combination therapy. The pilot feasibility study was conducted in preparation for this randomized controlled trial designed to assess the effect of an intervention.

Sex

All

Minimum age

18 Years

Maximum age

90 Years

Inclusion Criteria:

1. Diagnosis of Multiple Myeloma
2. Scheduled to start on Len-Dex therapy
3. Be ≥ 18 years of age
4. Able to provide written informed consent
5. Pre-clinical laboratory must meet the following criteria at enrollment

   * Platelet count \>50 × 109/L
   * Creatinine clearance (CrCl) \>15mL/min using Cockcroft-Gault Equation

Exclusion Criteria:

1. Major bleeding event within the previous 3 months prior to commencement of Len Dex therapy
2. Documented severe liver disease in the past 6 months (eg. acute clinical hepatitis, chronic active hepatitis, or cirrhosis)
3. Patient with a history of antiphospholipid syndrome especially if he/she is triple positive for lupus anticoagulant, anticardiolipin antibodies, and/or anti-b2 glycoprotein I antibodies.
4. A history of malignancy (with the exception of MM) within 2 years before randomization or any previously diagnosed malignancy with evidence of residual disease. Patients with a history of basal cell or squamous carcinoma are not excluded.
5. Patient with history of gastric or duodenal ulcer within 2 years
6. Plasma cell leukemia; systemic amyloidosis
7. Patient on therapeutic anticoagulation for treatment of VTE or ATE, or stroke prevention in non-valvular atrial fibrillation. Patients with a previous history of VTE who are not on any active anticoagulant therapy will not be excluded.
8. Patient on antiplatelet agents due to an absolute indication (e.g.; coronary stent, carotid stent).
9. Patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp such as ketoconazole, itraconazole, posaconazole or ritonavir)
10. Patient on single agent lenalidomide
11. Life expectancy less than 3 months as determined by the investigator.
12. Unstable medical or psychological condition that would interfere with trial participation, as determined by the investigator
13. Patient not able or not willing to give consent to participate in the study
14. Uncontrolled cardiovascular disease within 6 months prior to enrollment
15. Uncontrolled or poorly controlled diabetes or renal disease
16. Major surgery within 2 weeks before randomization
17. Known allergies, hypersensitivity, or intolerance to any of the study drugs.
18. Patients not able or not willing to give consent to participate in the Study.

• BACKGROUNDKamat AV Rivaroxaban Is an Effective and Well Tolerated Anti Thrombotic Agent in Patients on Lenalidomide Therapy and in Multiple Myeloma Blood 2014 124:5095;
• RESULTArain M, Campbell MJ, Cooper CL, Lancaster GA. What is a pilot or feasibility study? A review of current practice and editorial policy. BMC Med Res Methodol. 2010 Jul 16;10:67. doi: 10.1186/1471-2288-10-67. PMID 20637084
• RESULTLancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004 May;10(2):307-12. doi: 10.1111/j..2002.384.doc.x. PMID 15189396
• RESULTPalumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, Harousseau J, Zonder JA, Cavo M, Zangari M, Attal M, Belch A, Knop S, Joshua D, Sezer O, Ludwig H, Vesole D, Blade J, Kyle R, Westin J, Weber D, Bringhen S, Niesvizky R, Waage A, von Lilienfeld-Toal M, Lonial S, Morgan GJ, Orlowski RZ, Shimizu K, Anderson KC, Boccadoro M, Durie BG, Sonneveld P, Hussein MA; International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008 Feb;22(2):414-23. doi: 10.1038/sj.leu.2405062. Epub 2007 Dec 20. PMID 18094721
• RESULTAl-Ani F, Bermejo JM, Mateos MV, Louzada M. Thromboprophylaxis in multiple myeloma patients treated with lenalidomide - A systematic review. Thromb Res. 2016 May;141:84-90. doi: 10.1016/j.thromres.2016.03.006. Epub 2016 Mar 5. PMID 26986753
• RESULTLevine MN, Gu C, Liebman HA, Escalante CP, Solymoss S, Deitchman D, Ramirez L, Julian J. A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer. J Thromb Haemost. 2012 May;10(5):807-14. doi: 10.1111/j.1538-7836.2012.04693.x. PMID 22409262
• RESULTSchulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.