Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma (RithMM)

February 28, 2024 updated by: Lawson Health Research Institute

Rivaroxaban for Improvement of Thromboembolism Outcomes in Patients With Multiple Myeloma on Lenalidomide-based Therapy: RithMM Trial

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • London Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Len-Dex+Rivaroxaban
Patients with MM will receive Len-Dex combination and Rivaroxaban (10 mg) daily
Drug: Rivaroxaban
Rivaroxaban 10mg daily
Other Names:
  • Xarelto
Active Comparator: Len-Dex+ASA
Patients MM will receive Len-Dex combination and ASA 81 mg daily
Drug: ASA
ASA 81mg
Other Names:
  • aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of venous thromboembolic (VTE) and/or arterial thromboembolic (ATE) events in patients with Multiple Myeloma placed on the Rivaroxaban vs Aspirin after starting with Len-Dex therapy
Time Frame: 6 months
At each visit, patients will be asked standardized questions to capture the presence of primary. During these interviews the study coordinator will collect data related to resource utilization (e.g. health care services use) and ask whether the patient had a diagnosis of VTE, ATE or a bleeding event during this period. Any hospital or medical office encounters associated to any of the above-mentioned complaints will be checked and any test or procedures done will be recorded (e.g; echocardiogram, ECG, CT scan, MRI, transfusion).
6 months
Number of participants with treatment-related adverse events as assessed by CTCAE v6.0
Time Frame: 6 months
Frequency and severity of adverse events and serious AEs based on hospital admission and patient-self reporting events
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
External validation of the IMWG criteria for risk assessment of thromboembolic events in multiple myeloma patients
Time Frame: 6 months
Subgroup analysis stratifying patients into low and high risk of thromboembolic events to assess any potential difference in the efficacy and safety outcomes.
6 months
Assessment of correlation of between levels of biomarkers of myeloma and thrombosis with the risk of ATE or VTE
Time Frame: 6 months
The bio-markers are: D-dimer, LDH, B2 microglobulin and C-reactive protein (CRP) will be collected
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Collaborators

The Ottawa Hospital
Hamilton Health Sciences Corporation
Dalhousie University
Niagara Health System

Investigators

  • Principal Investigator: Martha Louzada, MD, Lawson Health Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 17, 2019

Primary Completion (Actual)

December 1, 2023

Study Completion (Estimated)

September 30, 2024

Study Registration Dates

First Submitted

September 21, 2016

First Submitted That Met QC Criteria

February 8, 2018

First Posted (Actual)

February 9, 2018

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 110804

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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