When this trial protocol was being developed in 2012, most Canadian patients did not have access to lenalidomide (Revlimid®) maintenance treatment. Through this trial, the MCRN was not only able to offer lenalidomide maintenance to newly-diagnosed patients following high-dose chemotherapy with autologous stem cell transplantation (ASCT), but also introduced a promising new tool for the management of myeloma – MRD or minimal residual disease. The trial also evaluated the efficacy of a modified conditioning regimen by adding busulfan to a lower dose of melphalan.
This Phase II trial was conducted in 10 Canadian centres. After bortezomib (Velcade®)-based induction, usually CyBorD (cyclophosphamide, bortezomib and dexamethasone), and in the absence of disease progression, patients received busulfan in combination with melphalan conditioning, followed by an ASCT. On day 100 post-ASCT, lenalidomide 10 mg/day was commenced, and escalated to 15 mg/day after 3 cycles (if appropriate), and continued until disease progression.
Dr Donna Reece
The Principal Investigator (PI) for this study is Dr Donna Reece of the Princess Margaret Cancer Centre in Toronto. A total of 77 patients have been enrolled in the following sites across Canada:
The study has been featured in poster presentations at several scientific meetings, including the American Society of Hematology (ASH) and the International Myeloma Workshop (IMW).
Led by Dr Nizar Bahlis in Calgary and Dr Christine Chen in Toronto, The STOMP Trial is playing a principal role in the clinical development of a promising new molecule, selinexor (KPT-330), a first-in-class selective inhibitor of nuclear export (SINE™) compound developed by Karyopharm Therapeutics. This has given eligible patients across Canada early access to the innovative therapy.
Dr Nizar Bahlis
The Phase II trial combines selinexor, with dexamethasone and a “backbone” therapy: either bortezomib (Velcade®), lenalidomide (Revlimid®) or pomalidomide (Pomalyst®) in patients with relapsed or refractory myeloma. The therapies are given orally, with the exception of bortezomib, which is given by subcutaneous injection.
More than 75 patients in the following Canadian centres have thus far participated in the trial:
Carfilzomib (Kyprolis®) is a new proteasome inhibitor that was approved by Health Canada in January 2016, but is not yet funded by any provincial drug plan. The KCd Trial provides access to this new drug to eligible patients with the triplet combination of carfilzomib, cyclophosphamide and dexamethasone. Cyclophosphamide is believed to have immunomodulatory properties and provides a more cost-effective alternative to other carfilzomib triplet combinations that have been studied.
The currently approved dosing schedule for carfilzomib is twice weekly. The trial is evaluating a once-weekly dosing regimen that will is more convenient for the patient and is also more cost-effective. The overall lower cost of this combination may help influence provincial drug funding decisions in the future.
The trial is being led by Dr Christopher Venner from the Cross Cancer Institute in Edmonton.
As of January 31, 2018, 76 patients out of a planned total of 76 have been recruited, and the trial is now closed.
A special mention goes to the Cross Cancer Institute, Maisonneuve-Rosemont Hospital and the Ottawa Hospital Research Institute who collectively accounted for more than half of total patient accrual.
Daratumumab (Darzalex®) is the first monoclonal antibody for the treatment of myeloma to be approved by Health Canada. Although daratumumab was approved by Health Canada on April 17, 2017, it is not yet covered by any of the provincial drug plans. For many patients in need, a clinical trial is one of the ways to access this treatment. LAURENTIANS will not only provide access to daratumumab for eligible patients across the country, but it will also answer the question of how to optimize the use of expensive drugs using a cost-effective approach.
Dr Michael Sebag
Led by Dr Michael Sebag at the McGill University Health Centre in Montreal, this open-label trial is planned to recruit a total of 120 patients across Canada into two study arms. One group will receive daratumumab, cyclophosphamide, dexamethasone and pomalidomide (Pomalyst®). The other group will receive the same treatment regimen, however pomalidomide will only be added when the participant’s disease progresses.
The trial was activated on October 25, 2017 and the following centres are open for recruitment:
Karyopharm Therapeutics has turned to Canada to lead a global Phase III randomized clinical trial (NCT03110562) that will evaluate the efficacy and safety of selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export (SINE™) compound.
This pivotal trial is led by Dr. Nizar Bahlis from the Arnie Charbonneau Cancer Institute of the University of Calgary in Alberta. The study will compare the combination of selinexor, bortezomib (Velcade®) and dexamethasone (SVd) versus the combination bortezomib and dexamethasone (Vd) in patients with relapsed or refractory myeloma who have had 1-3 prior lines of therapy.
BOSTON was designed based on data from the ongoing Phase II (MCRN 002) STOMP trial that has shown encouraging response data in the SVd combination arm, compared to historical response rates with the retreatment of a proteasome inhibitor (such as bortezomib) and dexamethasone alone. The results also included patients who were refractory to proteasome inhibitors. According to data presented at the 2016 American Society of Hematology annual meeting, SVd is well tolerated and its toxicity is manageable and similar to selinexor or bortezomib alone (monotherapy). The results also confirmed that selinexor demonstrates synergistic effects when combined with bortezomib.
The first Canadian patient was dosed with this regimen June 7, 2017 and a total of 362 patients will be recruited over the course of the trial across North America, Australia and Europe.
The following centres are open for patient recruitment:
How Selinexor Works
Selinexor binds with and inhibits the nuclear export protein XPO1 (also called CRM1), resulting in the accumulation of tumour suppressor protein inside cells. This leads to the reinitiation (and amplification) of the cell’s ability to suppress tumours, possibly by stimulating selective cell death (apoptosis) in cancer (myeloma) cells, generally sparing normal cells.
MCRN clinical trials are designed to meet patient needs, fill treatment gaps and answer important scientific question at the same time.
MCRN is strives to be a global leader in Real-Word Data Research in Multiple Myeloma with its national database platform
Number of Patients
Available Clinical Data
First Report of the Myeloma Canada Research Network (MCRN)-001 Trial UtilizingBortezomib-Based Induction, Enhanced Conditioning with IV Busulfan + Melphalan(BuMel) and Lenalidomide Maintenance: Feasibility of a National Canadian Study Basedon Achievement of Minimal Residual Disease (MRD) NegativityView PDF
Myeloma Canada Research Network (MCRN)-001 Trial Utilizing Bortezomib (btz)-Based Induction, Enhanced Conditioning with IV Busulfan + Melphalan (BuMel) and Lenalidomide (len) Maintenance in Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplant (ASCT): A National Canadian Study Evaluating Achievement of Minimal Residual Disease (MRD) Negativity and Involved Serum Hevylite chain (HLC) NormalizationView PDF
Myeloma Canada Research Network (MCRN) 001 Trial with Intravenous (IV) Busulfan + Melphalan (BuMel) as Enhanced Conditioning, followed by Lenalidomide (Len) Maintenance in Newly Diagnosed Multiple Myeloma (MM) Patients (Pts): First Results of Minimal Residual Disease (MRD) and Hevylite(TM) Chain (HLC) Assays at Day 100 Post Autologous Stem Cell Transplant (ASCT)View PDF
Selinexor in Combination with Bortezomib and Dexamethasone (SdB) Demonstrates Significant Activity in Patients with Refractory Multiple Myeloma (MM) Including Proteasome-Inhibitor Refractory Patients: Results of the Phase I Stomp TrialView PDF
Myeloma Canada Research Network (MCRN)-001 ASCT Study of Busulfan + Melphalan(BuMel) Conditioning Followed By Lenalidomide (Len) Maintenance: Updated ResultsIncluding Serial Minimal Residual Disease (MRD) and Involved Serum Hevylite™ Chain(HLC) Ratio AssessmentsView PDF
A single arm phase II study of high-dose weekly Carfilzomib plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma after 1-3 prior therapiesView PDF
The Myeloma Canada Research Network Canadian Multiple Myeloma Database (MCRN CMM-DB): Multi-Institutional Sharing Of Clinical Data For ResearchView PDF