MEET THE EXPERT: ENGIN GUL
DIRECTOR OF CLINICAL RESEARCH OPERATIONS, MCRN
Myeloma Canada: Engin, what brings you to Myeloma Canada and the Myeloma Canada Research Network? 
 
Engin Gul: For more than 9 years I was managing clinica l research operations in multiple myeloma both nationally and internationally. Prio r
to joining the MCRN, I was senio r project manager with the Multiple Myeloma Res earch Consortium (MMRC) at the Princess Margaret Cancer Centre where I gained unique insights into the clinical research operation of a non-profit research organization and its collaboration with various pharmaceutical partners and research institutions. When the Myeloma Canada Research Network was officially launched I was more than excited to join the team and share my knowledge and experience on a national scale.
 

MC: Can you explain the different phases of clinical trials and the types of trials the MCRN will be conducting?

EG:
The Myeloma Canada Research Network is currently focused on Phase I and Phase II clinical trials with an emphasis on developing trials based on research ideas proposed by members of the network across Canada.

Clinical trials are research studies involving people. Because people are involved, all clinical trials must be reviewed by Health Canada and shown to be safe. Clinical trials must also be approved by the Ethics Committees of all participating hospitals. These review processes are in place to protect the safety of participants. Only those studies that pass these rigourous approval processes are allowed to recruit patients. To answer this question, we must firstly define the four phases of clinical trials:

Phase I :
 
"What is the best and safest way to administer the new therapy?" A Phase I trial usually involves a small number of volunteers. The testing establishes the optimal dose for the new agent, and perhaps the best way to administer it (e.g. orally or intravenously).
Phase II:  
"Does the new agent work in a selected group of patients?" A Phase II trial typically involves a larger group of volunteers than a Phase I trial. Volunteers are usually chosen to reflect a particular type or stage of the disease. The goal is to evaluate how effective the new therapy is in treating the disease in this type of patient. Possible side effects are also monitored.
Phase III :
Only therapies that are effective, safe and have tolerable side effects can proceed to Phase III testing. Phase III trials compare the "standard of care" to the new treatment and are usually the largest, involving hundreds or even thousands of patients at cancer centres around the world.
Phase IV :
A Phase IV trial is sometimes referred to as "post marketing research". It is research on a drug that has already been approved and is being used widely.
 
 
MC: Can you tell us about MCRN's first trial?

EG : MCRN 001, or the "BuMel" trial, led by Dr Donna Reece of the Princess Margaret Cancer Centre, was designed to evaluate different strategies to improve the outcome of newly-diagnosed myeloma patients undergoing high-dose chemotherapy ("autologous stem cell transplant" or "ASCT").
 
A number of strategies have been proposed to improve the outcome of ASCT. The three main strategies are to incorporate novel agents into the induction regimen, using maintenance therapy following ASCT and the final strategy is to
enhance conditioning regimens.

MC: What does this study look like?

EG: The study protocol incorporates a novel agent based induction regimen (bortezomib) followed by an enhanced dose-adjusted conditioning regimen combining busulfan and melphalan (as opposed to the standard high-dose melphalan regimen) and adds lenalidomide maintenance post-ASCT until disease progression. The trial also incorporated minimal residual disease (MRD) measurement to better evaluate response and a correlative component based on the genomics analysis of tissue samples.

The trial opened in 2013 in 9 centres across Canada (see list below) with the Calgary team, led by Dr Nizar Bahlis and Dr Paola Neri, taking care of the genomics component. With a total projected recruitment of 78 patients, the trial has enrolled 76 patients and is expected to close for enrollment in the coming weeks.
 
It is important to emphasize the length of time it takes from when the initial idea is proposed to when the trial completes enrollment to when the final results are published. In the case of MCRN 001, the trial protocol was first presented five years ago and patients began to be enrolled three years ago. Although interim data analyses have been presented at scientific meetings such as ASH, the final results are still a few years away. Looking forward, our objective is to decrease the time required for protocol development and for enrollment.

Trials are very expensive, generally costing millions of dollars. This trial was made possible by the financial support provided by Otsuka and Celgene as well as the Southern Alberta Myeloma Patient Society (SAMPS) to support the genomics analysis and contributions by Myeloma Canada in support of the logistical requirements for the MRD and genomics components.

Participating sites:
  • Alberta
    • Cross Cancer institute, Edmonton
  • British Columbia
    • Vancouver General Hospital, Vancouver
  • New Brunswick
    • Saint John Regional Hospital, Saint John
  • Nova Scotia
    • Queen Elizabeth II Health Sciences Centre, Halifax
  • Ontario
    • London Regional Cancer Program, London
    • Ottawa Hospital Research Institute, Ottawa
    • Princess Margaret Cancer Centre, Toronto
  • Quebec
    • Maisonneuve-Rosemont Hospital, Montreal
    • Royal Victoria Hospital/McGill University, Montreal
  • Saskatchewan
    • Saskatoon Cancer Center, Saskatoon

MC: Which MCRN clinical trials are currently recruiting, and what is on the horizon?

EG: In addition to the MCRN001 trial, which has almost completed recruitment, we have two other trials that are currently open.

MCRN 002 (STOMP)
This trial, led by Dr Nizar Bahlis from Calgary and Dr Christine Chen from Toronto, is evaluating a promising new molecule, selinexor or KPT-330, a first-in-class Selective Inhibitor of Nuclear Export (SINE™) compound being developed by Karyopharm Therapeutics in Boston. The trial will combine selinexor with dexamethasone and a "backbone" therapy: either bortezomib, lenalidomide or pomalidomide in patients with relapsed or refractory myeloma. Through the MCRN's collaboration with Karyopharm, Canada is playing a leading global role in the clinical development of selinexor, giving Canadian patients early access to this promising new molecule. A total of 15 centres across Canada are participating in the trial (see below). With a projected enrollment of 201 patients, there are presently 38 patients participating in the trial.
 
Participating sites:
  • Alberta
    • Southern Alberta Cancer Research Institute, Calgary
    • Cross Cancer Institute, Edmonton
  • British Columbia
    • Vancouver General Hospital, Vancouver
  • Manitoba
    • CancerCare Manitoba, Winnipeg
  • Newfoundland and Labrador
    • Memorial Hospital of Newfoudland, St John's
  • Nova Scotia
    • Queen Elizabteh II Health Sciences Centre, Halifax
  • Ontario
    • Juravinski Cancer center, Hamilton
    • Ottawa Hospital Research Institute, Ottawa
    • Princess Margaret Cancer Centre, Toronto
    • University of Windsor/Windsor Regional Hospital, Windsor
  • Quebec
    • Maisonneuve-Rosemont Hospital, Montreal
    • Royal Victoria Hospital/McGill University, Montreal
    • L'Hôtel-Dieu de Québec, Quebec City
  • Saskatchewan
    • Saskatchewan Cancer Agency - Allan Blair Cancer Center, Regina
    • Saskatchewan Cancer center, Saskatoon
MCRN 003 (KCd)
The KCd (Kyprolis + Cyclophosphamide + dexamethasone) trial, led by Dr Andrew Belch and Dr Christopher Venner from Edmonton, will evaluate the efficacy of a weekly high-dose regimen of carfilzomib (Kyprolis) in combination with cyclophosphamide and low-dose dexamethasone in the treatment of patients with relapsed myeloma after one to three therapies. Presently, carfilzomib is given twice a week; a once weekly dosing schedule will not only be more convenient for the patient, it will also be more cost-effective.

The MCRN has partnered with the Canadian Clinical Trials Group (CCTG), an internationally recognized cancer research organization based at Queen's University in Kingston to support the national roll-out of the trial. Although the trial opened only a few weeks ago, three patients out of a total of 76 required have already enrolled.

Participating sites:
  • Alberta
    • Southern Alberta Cancer Research Institute, Calgary
    • Cross Cancer Institute, Edmonton
  • New Brunswick
    • Saint John Regional Hospital, Saint John
  • Nova Scotia
    • Queen Elizabeth II Health Sciences Centre, Halifax
  • Ontario
    • Cancer Centre of Southeastern Ontario, Kingston
    • Ottawa Hospital Research Institute, Ottawa
    • Princess Margaret Cancer Center, Toronto
  • Quebec
    • Maisonneuve-Rosemont, Montreal
    • L'Hôtel-Dieu de Québec, Quebec City
  • Saskatchewan
    • Saskatchewan Cancer Centre, Saskatoon
Future Trials
Currently, there are three other MCRN trials in different stages of development across the country: MCRN 004 (Dr Michael Sebag, Montreal); MCRN 005 (Dr Victor Zepeda, Calgary) and MCRN 006 (Dr Vishal Kukreti, Toronto). Each of these trials will focus on the promising area of immuno-oncology and evaluate new approaches to the treatment of myeloma.

MC: Thank you Engin for sharing your valuable insight. For additional information or questions, Engin can be reached at: egul@myeloma.ca
 
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