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The investigators will track 250 multiple myeloma patients across Canada over time, using new lab tests to evaluate their blood and bone marrow, as they receive standard of care treatment. The main hypothesis is that these tests will allow clinicians to better diagnose and manage multiple myeloma, improving patients' quality of life overall.
Multiple myeloma (MM) is a deadly cancer of the bone marrow that is challenging to manage and treat: the drugs that are currently available attack the cancer in the same way for everyone, but each patient has different types of MM cancer cells and different family traits that predict better or worse outcomes. As well, the ways in which clinicians test to see if the cancer is in remission are not very good at detecting small numbers of cancer cells still in the bone marrow after treatment - and which will, sooner or later cause the patient to get sick again. The goal of the M4 study is to improve MM patients' survival and quality of life over time, by finding better ways of a) characterizing each patient's experience with the disease, and b) identifying and tracking the small numbers of cells that remain after treatment.
The investigators plan to track 250 patients across Canada over time, who are getting treatment for multiple myeloma. While they are getting treatment, the research team will evaluate samples of their blood and bone marrow with newer, more precise laboratory tests. Participants will also be asked to take part in two scans of their bodies during their treatment. The investigators hypothesize that these tests can help clinicians make better treatment recommendations to patients.
The investigators will look at whether one test is better than another, or if a combination of these tests is needed to have the best information possible to make treatment decisions. At the same time, the research will also explore how and why some patients' cancer becomes resistant to the treatments over time, and how myeloma cells are able to start growing again after treatment. The research team will also collect information on how each patient's health and quality of life changes during and after treatment, and what are the associated costs with these new approaches - to both the healthcare system overall, and to patients.
Once the five-year research program is complete, it is hoped that clinicians will have a new, proven and affordable process of combining these new laboratory tests with the current clinical approach, to create new options to evaluate and treat multiple myeloma.
It is the overall goal that this research will make a difference, right away and across the world, in how doctors treat multiple myeloma, in how it is studied by scientists, and in how patients advocate for their own healthcare.
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| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity of Minimal Residual Disease (MRD) Assays | Comparison of the sensitivity of two leading-edge MRD assays - (1) multiparameter flow cytometry (MFC), and (2) immunoglobulin gene sequencing (IgS) - in patients who meet the conventional definition of complete remission post-treatment. | 100 days post-treatment |
| Sensitivity of Minimal Residual Disease (MRD) Assays | Comparison of the sensitivity of two leading-edge MRD assays - (1) multiparameter flow cytometry (MFC), and (2) immunoglobulin gene sequencing (IgS) - in patients who meet the conventional definition of complete remission post-treatment. | 12 months post-maintenance therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Sensitivity of MRD Assays with PET scans | Comparison of the sensitivity of two MRD assays - (1) multiparameter flow cytometry (MFC), and (2) immunoglobulin gene sequencing (IgS) - with (3) positron emission tomography (PET) imaging scans, in order to determine if PET scans offer additional information above and beyond that offered through the two assays. | 12 months post-maintenance therapy |
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Inclusion Criteria:
Exclusion Criteria:
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Patients will be recruited through hospital oncology clinics across Canada
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| Name | Affiliation | Role |
|---|---|---|
| Anthony J Reiman, MD | Horizon Health Network | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tom Baker Cancer Centre | Calgary | Alberta | T2N 4N2 | Canada | ||
| Cross Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Avet-Loiseau H, Corre J, Lauwers-Cances V, Chretien M, Robillard N, Leleu X, et al. 191 Evaluation of Minimal Residual Disease (MRD) By Next Generation Sequencing (NGS) Is Highly Predictive of Progression Free Survival in the IFM/DFCI 2009 Study. Blood 126(23): 191, 2015. | ||
| 25184863 | Background | Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, Banos A, Tiab M, Delforge M, Cavenagh J, Geraldes C, Lee JJ, Chen C, Oriol A, de la Rubia J, Qiu L, White DJ, Binder D, Anderson K, Fermand JP, Moreau P, Attal M, Knight R, Chen G, Van Oostendorp J, Jacques C, Ervin-Haynes A, Avet-Loiseau H, Hulin C, Facon T; FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014 Sep 4;371(10):906-17. doi: 10.1056/NEJMoa1402551. | |
| 24429703 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 26, 2017 | Nov 6, 2017 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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Human Peripheral Blood: DNA, RNA and WBC.
Human Bone Marrow: DNA, RNA, WBC, CD138 positive and CD138 negative cells.
| Predicting Progression-Free Survival Using MRD Assessment | Establish the prognostic significance of MRD assessment (i.e., the two MRD assays, and PET scans) on progression-free survival | 5 years |
| Predicting Overall Survival Using MRD Assessment | Establish the prognostic significance of MRD assessment (i.e., the two MRD assays, and PET scans) on overall survival | 5 years |
| Quality-Adjusted Life Years (QALYs) Gained | To fully understand health care costs and benefits associated with personalized risk-adapted testing and monitoring strategies for cancer, compared to current standard of care (e.g., non-personalized), the investigators will create a model that includes cohort's responses on patient-reported health status (using the EuroQol-5D or EQ-5D-L) and use of healthcare resources (using the NCIC Resource Utilization Form), and that will calculate quality-adjusted life years of the participants. | 5 years |
| Incremental Cost-Effectiveness of MRD Testing | To fully understand health care costs and benefits associated with personalized risk-adapted testing and monitoring strategies for cancer, compared to current standard of care (e.g., non-personalized), the investigators will create a model that includes cohort's responses on patient-reported health status (using the EuroQol-5D or EQ-5D-L) and use of healthcare resources (using the NCIC Resource Utilization Form), and that will calculate the cost-effectiveness of the MRD assays under investigation. | 5 years |
| Productivity Costs Associated with MRD Testing | To fully understand health care costs and benefits associated with personalized risk-adapted testing and monitoring strategies for cancer, compared to current standard of care (e.g., non-personalized), the investigators will create a model that includes cohort's responses on patient-reported health status (using the EuroQol-5D or EQ-5D-L) and use of healthcare resources (using the NCIC Resource Utilization Form), and that will calculate the individual and system-level productivity costs associated with the MRD assays under investigation. | 5 years |
| Multiple Myeloma Patients' Quality of Life (QOL) | The investigators will evaluate patients' QOL, especially how it is impacted by treatment, disease and patient characteristics, using a common self-report measure (European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire, or EORTC-QLQ-30). Specific outcomes include QOL at each time point in the study and overall for the cohort, comparing those who achieve MRD and those who do not. | 5 years |
| Correlative Study: Sensitivity and Specificity of Drug Resistance Assays | The investigators will also investigate sensitivity and specificity of assays of drug resistance (e.g., why this cancer eventually becomes resistant to the drugs used to treat it) | 5 years |
| Correlative Study: Circulating Tumor DNA | The investigators will also investigate prognostic significance of circulating tumour (ct) DNA profiles | 5 years |
| Correlative Study: Describing Myeloma Progenitor Populations | The investigators will also seek to understand how the cancer recurs and regrows, even for those who achieve an MRD state. | 5 years |
| Edmonton |
| Alberta |
| T6G 1Z2 |
| Canada |
| Vancouver General Hospital | Vancouver | British Columbia | V5Z 1M9 | Canada |
| CancerCare Manitoba | Winnipeg | Manitoba | R3E 0V9 | Canada |
| Saint John Regional Hospital (Horizon Health Network) | Saint John | New Brunswick | E2L 4L5 | Canada |
| Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia | B3H 2Y9 | Canada |
| Buland Mangukia | Hamilton | Ontario | L8V 1C3 | Canada |
| Princess Margaret Cancer Centre | Toronto | Ontario | M5G 1X6 | Canada |
| McGill University Health Centre | Montreal | Quebec | H4A 3J1 | Canada |
| Background |
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| 23974982 | Background | Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, Miguel JS, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H; International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014 Feb;28(2):269-77. doi: 10.1038/leu.2013.247. Epub 2013 Aug 26. |
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| 26181891 | Background | Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. doi: 10.1001/jamaoncol.2015.2010. |
| 27511158 | Background | Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6. |
| 28854350 | Background | Leung-Hagesteijn C, Erdmann N, Cheung G, Keats JJ, Stewart AK, Reece DE, Chung KC, Tiedemann RE. Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma. Cancer Cell. 2015 Oct 12;28(4):541-542. doi: 10.1016/j.ccell.2015.09.010. Epub 2015 Oct 12. No abstract available. |
| 25622976 | Background | Mailankody S, Korde N, Lesokhin AM, Lendvai N, Hassoun H, Stetler-Stevenson M, Landgren O. Minimal residual disease in multiple myeloma: bringing the bench to the bedside. Nat Rev Clin Oncol. 2015 May;12(5):286-95. doi: 10.1038/nrclinonc.2014.239. Epub 2015 Jan 27. |
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| 18172311 | Background | Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, McNiece I, Lin L, Ambinder RF, Peacock C, Watkins DN, Huff CA, Jones RJ. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008 Jan 1;68(1):190-7. doi: 10.1158/0008-5472.CAN-07-3096. |
| 28686535 | Background | Moreau P, Attal M, Caillot D, Macro M, Karlin L, Garderet L, Facon T, Benboubker L, Escoffre-Barbe M, Stoppa AM, Laribi K, Hulin C, Perrot A, Marit G, Eveillard JR, Caillon F, Bodet-Milin C, Pegourie B, Dorvaux V, Chaleteix C, Anderson K, Richardson P, Munshi NC, Avet-Loiseau H, Gaultier A, Nguyen JM, Dupas B, Frampas E, Kraeber-Bodere F. Prospective Evaluation of Magnetic Resonance Imaging and [18F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study. J Clin Oncol. 2017 Sep 1;35(25):2911-2918. doi: 10.1200/JCO.2017.72.2975. Epub 2017 Jul 7. |
| 23238036 | Background | Nygaard AD, Garm Spindler KL, Pallisgaard N, Andersen RF, Jakobsen A. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer. Lung Cancer. 2013 Mar;79(3):312-7. doi: 10.1016/j.lungcan.2012.11.016. Epub 2012 Dec 11. |
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |