RithMM: ASA vs. Rivaroxaban in Newly Diagnosed or Relapsed and Refractory Multiple Myeloma Patients Treated With Len-Dex Combination Therapy.

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT03428373

Collaborator

The Ottawa Hospital (Other), Dalhousie University (Other), St. Boniface Hospital (Other), Hamilton Health Sciences Corporation (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The intended pilot study is designed as a 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

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

The investigators will perform a pragmatic multicentre open label pilot randomized controlled trial in Canada (London, Hamilton, Ottawa, Halifax, Winnipeg ) to assess the feasibility of a full RCT to compare the efficacy and safety of Rivaroxaban or ASA in preventing venous or arterial thromboembolic events in patients with myeloma on Len-Dex based therapy. For the data collection the research team will use REDCap which is a Research Electronic Data Capture web-based tool for creating and managing online database applications and surveys. System will allow performing the randomization as well. Patients will be randomized to ASA 81 mg daily or Rivaroxaban 10 mg daily. Patients will enter the study at the time of commencement of anticoagulants (Rvaroxaban or ASA) and be followed for 6 months, or until 4 weeks after stopping Len-Dex, or they withdraw from the study, or they leave the province, or die, whichever comes first. Patients will be randomly assigned, in a 1: 1 ratio, to receive either Rivaroxaban 10 mg daily for 6 months or ASA 81 mg daily for 6 months. A web-based randomization system will ensure allocation concealment. Randomization will be stratified by site and by line of therapy (first line or other) in blocks of 4. Using a vanguard design, the research team intends to rollover the participants of our feasibility study into a full randomized control trial comparing the efficacy and safety of Rivaroxaban or ASA in preventing venous or arterial thromboembolic events (ATE) in myeloma patients receiving Len-Dex therapy. For the full RCT, the investigators plan to externally validate the IMWG criteria model for thromboembolic risk. The investigators will also evaluate the impact of adding myeloma bio-markers to the IMWG criteria to assess their association with TE risk and potentially improve the utility and generalizability of the IMWG criteria. The bio-markers are: D-dimer, LDH, B2 microglobulin and C-reactive protein (CRP). All of the IMWG criteria risk factors and the bio-markers will be collected for the participants of the feasibility study for potential future enrollment into the full RCT.

Study Design

Study Type:

Interventional

Anticipated 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

Actual Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Mar 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Thrombosis assessment of patients with Multiple Myeloma placed on the Rivaroxaban vs Aspirin [6 months]
Participants that develop symptoms of venous or arterial thromboembolism will be assessed as per standard of care such as Doppler ultrasound for deep venous thrombosis ad CTPA or V/Q lung scan for Pulmonary embolism; and appropriate cardiac interventions for coronary events.

Secondary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [6 months]
Frequency and severity of adverse events and serious AEs based on hospital admission and patientself reporting events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients with NDMM or RRMM
Must be receiving Len-Dex based treatment

Exclusion Criteria:

Creatinine clearance (CrCl) is less than 15mL/min;
Platelet count is less than 50,000;
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
Major bleeding event within the previous 3 months prior to the Len-Dex therapy;
previous recent anticoagulation or on antiplatelet therapy
previous lenalidomide maintenance therapy
known allergies to any of the study drugs
history of gastric or duodenal ulcer