Back to results

Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma (RithMM)

Primary Purpose

Multiple Myeloma in Relapse, Multiple Myeloma Progression, Multiple Myeloma Stage II

Status

Recruiting

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Rivaroxaban

ASA

About this trial

This is an interventional treatment trial for Multiple Myeloma in Relapse focused on measuring Multiple Myeloma

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

Major bleeding event within the previous 3 months prior to commencement of Len Dex therapy
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
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).
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
Major surgery within 2 weeks before randomization
Known allergies, hypersensitivity, or intolerance to any of the study drugs

Sites / Locations

London Health Sciences CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Len-Dex+Rivaroxaban

Len-Dex+ASA

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

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

Secondary Outcome Measures

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

Subgroup analysis stratifying patients into low and high risk of thromboembolic events to assess any potential difference in the efficacy and safety outcomes.

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

The bio-markers are: D-dimer, LDH, B2 microglobulin and C-reactive protein (CRP) will be collected

Full Information

NCT ID

NCT03428373

First Posted

September 21, 2016

Last Updated

October 3, 2022

Sponsor

Lawson Health Research Institute

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03428373

Brief Title

Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma

Acronym

RithMM

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 30, 2023 (Anticipated)

Primary Completion Date

December 1, 2024 (Anticipated)

Study Completion Date

July 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lawson Health Research Institute

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

86 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Len-Dex+Rivaroxaban

Arm Type

Experimental

Arm Description

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

Arm Title

Len-Dex+ASA

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rivaroxaban

Other Intervention Name(s)

Xarelto

Intervention Description

Rivaroxaban 10mg daily

Intervention Type

Drug

Intervention Name(s)

ASA

Other Intervention Name(s)

aspirin

Intervention Description

ASA 81mg

Primary Outcome Measure Information:

Title

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

Description

Time Frame

6 months

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v6.0

Description

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

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

Description

Subgroup analysis stratifying patients into low and high risk of thromboembolic events to assess any potential difference in the efficacy and safety outcomes.

Time Frame

6 months

Title

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

Description

The bio-markers are: D-dimer, LDH, B2 microglobulin and C-reactive protein (CRP) will be collected

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility 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 Platelet count >50 × 109/L AST <2.5x ULN ALT <2.5x ULN Total Bilirubin <2.0 xULN Creatinine clearance (CrCl) >15mL/min using Cockcroft-Gault Equation Able to provide written informed consent Exclusion Criteria: Major bleeding event within the previous 3 months prior to commencement of Len Dex therapy 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 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). 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 Major surgery within 2 weeks before randomization Known allergies, hypersensitivity, or intolerance to any of the study drugs

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Martha Louzada, MD MSc (Epid)

Phone

519-685-8500

Ext

52391

Martha.Louzada@lhsc.on.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Kate Kelly, MSc MPH/Gero

Phone

519-685-8500

Ext

53639

kate.kelly@lhsc.on.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Martha Louzada, MD

Organizational Affiliation

Lawson Health Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

London Health Sciences Centre

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 5W9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Maisam Abouzeenni

Phone

5196858500

Ext

56840

maisam.abouzeenni@lhsc.on.ca

First Name & Middle Initial & Last Name & Degree

Terryl Angle

Phone

519-685-8500

Ext

57135

terryl.angle@lhsc.on.ca

12. IPD Sharing Statement

Plan to Share IPD

Citations:

Citation

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;

Results Reference

background

PubMed Identifier

20637084

Citation

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.

Results Reference

result

PubMed Identifier

15189396

Citation

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.

Results Reference

result

PubMed Identifier

18094721

Citation

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.

Results Reference

result

PubMed Identifier

26986753

Citation

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.

Results Reference

result

PubMed Identifier

22409262

Citation

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.

Results Reference

result

PubMed Identifier

15842354

Citation

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.

Results Reference

result

PubMed Identifier

23903204

Citation

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.

Results Reference

result

PubMed Identifier

34582035

Citation

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.

Results Reference

derived

Learn more about this trial

Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma

We'll reach out to this number within 24 hrs