Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma

NCT03428373 | Active Not Recruiting Phase 2

• 1 other identifier: 110804
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma Progression; Multiple Myeloma Stage II; Multiple Myeloma Stage I; Multiple Myeloma With Failed Remission; Multiple Myeloma Stage III

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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

  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

  Frequency and severity of adverse events and serious AEs based on hospital admission and patient-self reporting events

  6 months

Secondary Outcomes (2)

• External validation of the IMWG criteria for risk assessment of thromboembolic events in multiple myeloma patients

  6 months

• Assessment of correlation of between levels of biomarkers of myeloma and thrombosis with the risk of ATE or VTE

  6 months

Study Arms (2)

Len-Dex+Rivaroxaban

EXPERIMENTAL

Patients with MM will receive Len-Dex combination and Rivaroxaban (10 mg) daily

Drug: Rivaroxaban

Len-Dex+ASA

ACTIVE COMPARATOR

Patients MM will receive Len-Dex combination and ASA 81 mg daily

Drug: ASA

Interventions

Rivaroxaban DRUG

Rivaroxaban 10mg daily

Also known as: Xarelto

Len-Dex+Rivaroxaban

ASA DRUG

ASA 81mg

Also known as: aspirin

Len-Dex+ASA

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Multiple Myeloma
• Scheduled to start on Len-Dex therapy
• Be ≥ 18 years of age
• Able to provide written informed consent
• Pre-clinical laboratory must meet the following criteria at enrollment
• Platelet count \>50 × 109/L
• Creatinine clearance (CrCl) \>15mL/min using Cockcroft-Gault Equation

You may not qualify if:

• Major bleeding event within the previous 3 months prior to commencement of Len Dex therapy
• Documented severe liver disease in the past 6 months (eg. acute clinical hepatitis, chronic active hepatitis, or cirrhosis)
• 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.
• 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.
• Patient with history of gastric or duodenal ulcer within 2 years
• Plasma cell leukemia; systemic amyloidosis
• 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.
• Patient on antiplatelet agents due to an absolute indication (e.g.; coronary stent, carotid stent).
• Patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp such as ketoconazole, itraconazole, posaconazole or ritonavir)
• Patient on single agent lenalidomide
• Life expectancy less than 3 months as determined by the investigator.
• Unstable medical or psychological condition that would interfere with trial participation, as determined by the investigator
• Patient not able or not willing to give consent to participate in the study
• Uncontrolled cardiovascular disease within 6 months prior to enrollment
• Uncontrolled or poorly controlled diabetes or renal disease

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• The Ottawa Hospital: collaborator
• Dalhousie University: collaborator
• Niagara Health System: collaborator
• Hamilton Health Sciences Corporation: collaborator

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Related Publications (9)

• 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;

  BACKGROUND

• Arain 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 RESULT

• Lancaster 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 RESULT

• Palumbo 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 RESULT

• Al-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 RESULT

• Levine 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 RESULT

• Schulman 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.

  PMID: 15842354 RESULT

• Leleu X, Rodon P, Hulin C, Daley L, Dauriac C, Hacini M, Decaux O, Eisemann JC, Fitoussi O, Lioure B, Voillat L, Slama B, Al Jijakli A, Benramdane R, Chaleteix C, Costello R, Thyss A, Mathiot C, Boyle E, Maloisel F, Stoppa AM, Kolb B, Michallet M, Lamblin A, Natta P, Facon T, Elalamy I, Fermand JP, Moreau P. MELISSE, a large multicentric observational study to determine risk factors of venous thromboembolism in patients with multiple myeloma treated with immunomodulatory drugs. Thromb Haemost. 2013 Oct;110(4):844-51. doi: 10.1160/TH13-02-0140. Epub 2013 Aug 1.

  PMID: 23903204 RESULT

• Kahale LA, Matar CF, Tsolakian I, Hakoum MB, Yosuico VE, Terrenato I, Sperati F, Barba M, Hicks LK, Schunemann H, Akl EA. Antithrombotic therapy for ambulatory patients with multiple myeloma receiving immunomodulatory agents. Cochrane Database Syst Rev. 2021 Sep 28;9(9):CD014739. doi: 10.1002/14651858.CD014739.

  PMID: 34582035 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Rivaroxaban; Aspirin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Martha Louzada, MD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: February 9, 2018
• Study Start: January 17, 2019
• Primary Completion: December 1, 2023
• Study Completion: September 30, 2024
• Last Updated: February 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)