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Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma (RithMM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03428373
Recruitment Status : Recruiting
First Posted : February 9, 2018
Last Update Posted : October 5, 2022
Sponsor:
Collaborators:
The Ottawa Hospital
Dalhousie University
Niagara Health System
Hamilton Health Sciences Corporation
Information provided by (Responsible Party):
Lawson Health Research Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma in Relapse Multiple Myeloma Progression Multiple Myeloma Stage II Multiple Myeloma Stage I Multiple Myeloma With Failed Remission Multiple Myeloma Stage III Drug: Rivaroxaban Drug: ASA Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Rivaroxaban for Improvement of Thromboembolism Outcomes in Patients With Multiple Myeloma on Lenalidomide-based Therapy: RithMM Trial
Estimated Study Start Date : July 30, 2023
Estimated Primary Completion Date : December 1, 2024
Estimated Study Completion Date : July 30, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Rivaroxaban

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 Name: Xarelto

Active Comparator: Len-Dex+ASA
Patients MM will receive Len-Dex combination and ASA 81 mg daily
Drug: ASA
ASA 81mg
Other Name: aspirin




Primary Outcome Measures :
  1. 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).

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Multiple Myeloma
  • Scheduled to start on Len-Dex therapy
  • Be ≥ 18 years of age
  • 4. Pre-clinical laboratory must meet the following criteria at enrollment

    1. Platelet count >50 × 109/L
    2. AST <2.5x ULN
    3. ALT <2.5x ULN
    4. Total Bilirubin <2.0 xULN
    5. Creatinine clearance (CrCl) >15mL/min using Cockcroft-Gault Equation
  • Able to provide written informed consent

Exclusion Criteria:

  1. Major bleeding event within the previous 3 months prior to commencement of Len Dex therapy
  2. 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.
  3. Patient with history of gastric or duodenal ulcer within 2 years
  4. 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.
  5. Patient on antiplatelet agents due to an absolute indication (e.g.; coronary stent, carotid stent).
  6. Patient on single agent lenalidomide
  7. Life expectancy less than 3 months as determined by the investigator
  8. Unstable medical or psychological condition that would interfere with trial participation, as determined by the investigator
  9. Patient not able or not willing to give consent to participate in the study
  10. Uncontrolled cardiovascular disease within 6 months prior to enrollment
  11. Uncontrolled or poorly controlled diabetes or renal disease
  12. Major surgery within 2 weeks before randomization
  13. Known allergies, hypersensitivity, or intolerance to any of the study drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03428373


Contacts
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Contact: Martha Louzada, MD MSc (Epid) 519-685-8500 ext 52391 Martha.Louzada@lhsc.on.ca
Contact: Kate Kelly, MSc MPH/Gero 519-685-8500 ext 53639 kate.kelly@lhsc.on.ca

Locations
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Canada, Ontario
London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A 5W9
Contact: Maisam Abouzeenni    5196858500 ext 56840    maisam.abouzeenni@lhsc.on.ca   
Contact: Terryl Angle    519-685-8500 ext 57135    terryl.angle@lhsc.on.ca   
Sponsors and Collaborators
Lawson Health Research Institute
The Ottawa Hospital
Dalhousie University
Niagara Health System
Hamilton Health Sciences Corporation
Investigators
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Principal Investigator: Martha Louzada, MD Lawson Health Research Institute
Publications of Results:

Other Publications:
Kamat AV Rivaroxaban Is an Effective and Well Tolerated Anti Thrombotic Agent in Patients on Lenalidomide Therapy and in Multiple Myeloma Blood 2014 124:5095;

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT03428373    
Other Study ID Numbers: 110804
First Posted: February 9, 2018    Key Record Dates
Last Update Posted: October 5, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lawson Health Research Institute:
Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Rivaroxaban
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Anticoagulants