Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass)

A Prospective, Longitudinal, Observational Study in Newly Diagnosed Multiple Myeloma (MM) Patients to Assess the Relationship Between Patient Outcomes, Treatment Regimens and Molecular Profiles

The primary objective of this observational study is to identify the molecular profiles and clinical characteristics that define subsets of myeloma patients during the course of the disease.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma

Detailed Description

Understanding the molecular basis of cancer is a critical step toward devising the most effective treatment of the patient as an individual. The promise of molecular targeted therapeutics and personalized cancer care has been demonstrated in breast and lung cancer and chronic myeloid leukemia. However, similar examples of success in multiple myeloma have not been achieved despite extensive basic research as well as clinical advances. What is well understood is that myeloma is a heterogeneous disease with great genetic and epigenetic complexity.22, 23 Therefore, there remains a critical need to understand myeloma patient biology in the context of current patient care.24 The objective of this longitudinal study is to identify patient subgroups and phenotypes defined by molecular profiling and clinical features. These profiles will enable a better understanding of mechanisms of disease, drug response and patient relapse. Ultimately the study is intended to drive successful drug development and patient care in multiple myeloma.

• Study Type: Observational
• Enrollment (Actual): 1154

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Tom Baker Cancer Centre, Alberta Health Services
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute, Alberta Health Services
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3A1A1
      • McGill University Health Center, Royal Victoria Hospital
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial
  • Barcelona, Spain, 08026
    • Hospital Santa Creu i Sant Pau
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28222
    • Hospital Puerta de Hierro
  • Aragón
    • Zaragoza, Aragón, Spain, 50012
      • Hospital Clinica Universitari Lozano Blesa
  • Castilla-León
    • Salamanca, Castilla-León, Spain, 37007
      • Hospital University de Salamanca
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • H. U. Germans Trias i Pujol
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07120
      • Hospital Univ Son Espases
    • Palma de Mallorca, Islas Baleares, Spain, 07198
      • Hospital Son Llàtze
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Quiron de Madrid
    • San Sebastián de los Reyes, Madrid, Spain, 28702
      • University Hospital Infanta Sofia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
  • Santa Cruz
    • Tenerife, Santa Cruz, Spain, 38320
      • Hospital Universitari de Canarias
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Campus in Scottsdale, AZ
  • California
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System
    • San Diego, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • San Diego, California, United States, 92123
      • SHARP Health Care
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente of Colorado
  • Connecticut
    • Stamford, Connecticut, United States, 06907
      • Carl and Dorothy Bennett Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • VA Medical Center, Washington DC,
  • Florida
    • Ocala, Florida, United States, 34471
      • Ocala Oncology Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute - Emory University
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
  • Maryland
    • Salisbury, Maryland, United States, 21801
      • Peninsula Regional Cancer Center
    • Silver Spring, Maryland, United States, 20902
      • Holy Cross Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic-Rochester
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03784
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
  • New York
    • Bronx, New York, United States, 10469
      • Eastchester Center for Cancer Care
    • Johnson City, New York, United States, 13790
      • Broome Oncology
    • New York, New York, United States, 10016
      • New York University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mt Sinai Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College-NY Presbyterian Hospital
    • Roslyn, New York, United States, 11576
      • St Francis Hospital
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hematology Oncology
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Pinehurst, North Carolina, United States, 28374
      • First Health Outpatient Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Tualatin, Oregon, United States, 97062
      • Northwest Cancer Specialists, PC
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Research Institute
    • Dallas, Texas, United States, 75390
      • University of Texas Southwest Medical Center
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas
    • Temple, Texas, United States, 76504
      • Central Texas VA Healthcare Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
    • Waco, Texas, United States, 76712
      • Texas Oncology- Waco
  • Virginia
    • Fairfax, Virginia, United States, 22013
      • Virginia Cancer Specialists PV
  • Washington
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital/North Star Lodge
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed, symptomatic, multiple myeloma, candidates for systemic treatment

Description

Inclusion Criteria:

• Patient is at least 18 years old.
• Patient has been diagnosed with symptomatic MM with measurable disease that includes at least one of the following:

Serum M protein ≥ 1g/dl Urine M protein ≥ 200 mg/24 hrs Involved free light chain level ≥ 10 mg/dl and an abnormal serum free light chain ratio (<0.26 or >1.65).

• The patient is a candidate for systemic therapy that includes an IMiD® (e.g., lenalidomide, pomalidomide, thalidomide) and/or proteasome inhibitor (e.g., bortezomib, carfilzomib) as part of the initial regimen.
• No more than 30 days from baseline bone marrow evaluation as per this protocol to initiation of first-line therapy.
• Patient has read, understood and signed informed consent.

Exclusion Criteria:

• Patient is already receiving systemic therapy for MM (a single dose of bisphosphonates and up to 100 mg total dose of dexamethasone or equivalent corticosteroids are permitted prior to registration on study).
• Patient had another malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix).
• Patient is enrolled in a blinded clinical trial for the first-line treatment of multiple myeloma. Patients may be enrolled in subsequent clinical trials as long as continued access to data and tissue, as per this protocol, is not prohibited.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Newly diagnosed Multiple Myeloma; This is a prospective observational study in patients with symptomatic multiple myeloma who have not yet initiated therapy for their disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular profiles and clinical characteristics that define subsets of myeloma patients at initial diagnosis and at relapse of disease.	Standard clinical and laboratory assessments. Genomic tests (DNA and RNA sequencing, etc.) on bone marrow aspirates obtained at baseline, suspected complete response, and relapse/progression.	Baseline to 8 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rates	IMWG criteria: stringent complete response, complete response, very good partial response, partial response, no response.	Up to one year after baseline.
Survival rates	Progression-free survival and overall survival	Five to eight years after baseline
Bone disease assessed radiographically		Baseline and during five to eight years of follow-up
Health-related quality of life	EORTC QLQ-C30 and QLQ-MY20	Baseline and during five to eight years of follow-up
Resource utilization	Hospitalizations and ER visits	Baseline and during five to eight years of follow-up
Severe adverse events	Severe/CTCAE grade 3-4 adverse events (checklist)	Five to eight years

Collaborators and Investigators

• Sponsor: Multiple Myeloma Research Foundation
• Collaborators: Spectrum Health Hospitals; Translational Genomics Research Institute; Van Andel Research Institute
• Investigators: Study Director: Daniel Auclair, Multiple Myeloma Research Foundation

Publications and helpful links

General Publications

• Auclair D, Mansfield C, Fiala MA, Chari A, Cole CE, Kaufman JL, Orloff GJ, Siegel DS, Zonder JA, Mange B, Yesil J, Dalal M, Mikhael JR. Preferences and Priorities for Relapsed Multiple Myeloma Treatments Among Patients and Caregivers in the United States. Patient Prefer Adherence. 2022 Mar 1;16:573-585. doi: 10.2147/PPA.S345906. eCollection 2022.
• Barwick BG, Gupta VA, Matulis SM, Patton JC, Powell DR, Gu Y, Jaye DL, Conneely KN, Lin YC, Hofmeister CC, Nooka AK, Keats JJ, Lonial S, Vertino PM, Boise LH. Chromatin Accessibility Identifies Regulatory Elements Predictive of Gene Expression and Disease Outcome in Multiple Myeloma. Clin Cancer Res. 2021 Jun 1;27(11):3178-3189. doi: 10.1158/1078-0432.CCR-20-2931. Epub 2021 Mar 17.
• Foltz SM, Gao Q, Yoon CJ, Sun H, Yao L, Li Y, Jayasinghe RG, Cao S, King J, Kohnen DR, Fiala MA, Ding L, Vij R. Evolution and structure of clinically relevant gene fusions in multiple myeloma. Nat Commun. 2020 May 29;11(1):2666. doi: 10.1038/s41467-020-16434-y.
• Miller A, Asmann Y, Cattaneo L, Braggio E, Keats J, Auclair D, Lonial S; MMRF CoMMpass Network; Russell SJ, Stewart AK. High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma. Blood Cancer J. 2017 Sep 22;7(9):e612. doi: 10.1038/bcj.2017.94.

Helpful Links

• The Multiple Myeloma Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: October 7, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimated): October 19, 2011

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Observational; Longitudinal; Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: MMRF-11-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Interim Analysis data will be released every 6 months