Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma (RithMM)

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Full Title:
Rivaroxaban for Improvement of Thromboembolism Outcomes in Patients With Multiple Myeloma on Lenalidomide-based Therapy: RithMM Trial
Myeloma stage or condition:
Multiple Myeloma in Relapse Multiple Myeloma Progression Multiple Myeloma Stage II Multiple Myeloma Stage I Multiple Myeloma With Failed Remission Multiple Myeloma Stage III
Study phase:
Phase 2/Phase 3
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.
Detailed Description:
RithMM is a phase IV, pragmatic, multicenter, open label Canadian trial. The study started with a pilot feasibility phase where 3 centres (London, Ottawa and Halifax) enrolled 34 patients within 12 months. Utilizing a roll-over design, the full RithMM trial will require a total of 304 patients to demonstrate that rivaroxaban 10 mg daily for 6 months is superior to ASA 81 mg daily for 6 months in preventing any thromboembolic events in newly diagnosed myeloma (NDMM) and relapsed/refractory (RRMM) patients on Len-Dex -based therapy. The study will require 8 participating centres in order to be able to achieve our recruitment goal within 12 to 18 months. Patients with NDMM or RRMM receiving Len-Dex based combination therapy with or without combination with other anti-myeloma drugs will be assessed for eligibility to be enrolled in the study. The research team intends to rollover the participants of our feasibility study into this current full randomized control trial comparing the efficacy outcome for the RithMM trial is the overall incidence of cardiovascular events, which includes arterial or venous thromboembolic events. By conducting this trial, the investigators plan to externally validate the International Myeloma Working Group (IMWG) criteria model for thromboembolic risk by assessing the relevance of measuring pre-specified myeloma and thrombosis activity biomarkers (D-Dimer, beta-2 microglobulin, C-reactive protein (CRP), LDH) at every follow-up visit and their potential association with thromboembolism (TE) risk.
Drug : Rivaroxaban

Rivaroxaban 10mg daily

Drug : ASA

ASA 81mg

Study Arms:
Experimental : Len-Dex+Rivaroxaban
Patients with MM will receive Len-Dex combination and Rivaroxaban (10 mg) daily
Active Comparator : Len-Dex+ASA
Patients MM will receive Len-Dex combination and ASA 81 mg daily
Study Type:
Study Design:
Allocation: Randomized
Intervention Model: Factorial Assignment
Primary Purpose: Treatment
Masking: None (Open Label)
Recruitment status:
Active, not recruiting
Eligibility criteria:
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.
Locations / Centres:

London Health Sciences Centre, London, Ontario – ()

Not available
First posted:
Actual start date:
January 17, 2019
Last updated:
Estimated enrollment:
Estimated completion date:
Estimated primary completion date:
Multiple Myeloma in Relapse
Multiple Myeloma Progression
Multiple Myeloma Stage II
Multiple Myeloma Stage I
Multiple Myeloma With Failed Remission
Multiple Myeloma Stage III
18 Years-90 Years
Accepts healthy volunteers:
Listed location countries:
NCT number:
Other study ID numbers:
Has Data monitoring committee:
U.S. FDA-regulated product:
IPD Sharing Statement :
Responsible party:
Study sponsor:
The Ottawa Hospital
Dalhousie University
Niagara Health System
Hamilton Health Sciences Corporation
Lawson Health Research Institute
Martha Louzada, MD Lawson Health Research Institute
Protocol Registration and Results System:
Verification date: