Clinical trial NCT01454297: Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile
Official title: A Prospective, Longitudinal, Observational Study in Newly Diagnosed Multiple Myeloma (MM) Patients to Assess the Relationship Between Patient Outcomes, Treatment Regimens and Molecular Profiles
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Myeloma
Keywords: Myeloma
Multiple Myeloma
Observational
Longitudinal
Lead sponsor: Multiple Myeloma Research Foundation
Sponsor class: OTHER
Collaborators: name: Translational Genomics Research Institute
name: Spectrum Health Hospitals
name: Van Andel Research Institute
First posted: 2011-10-19
Enrollment: 1154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly diagnosed, symptomatic, multiple myeloma, candidates for systemic treatment

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Molecular profiles and clinical characteristics that define subsets of myeloma patients at initial diagnosis and at relapse of disease.
timeFrame: Baseline to 8 years.
Secondary outcomes:
measure: Response rates
timeFrame: Up to one year after baseline.
measure: Survival rates
timeFrame: Five to eight years after baseline
measure: Bone disease assessed radiographically
timeFrame: Baseline and during five to eight years of follow-up
measure: Health-related quality of life
timeFrame: Baseline and during five to eight years of follow-up
measure: Resource utilization
timeFrame: Baseline and during five to eight years of follow-up
measure: Severe adverse events
timeFrame: Five to eight years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Campus in Scottsdale, AZ
state: Arizona
city: San Diego
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: San Diego
country: United States
facility: Sharp Health Care
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Denver
country: United States
facility: Kaiser Permanente of Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Stamford
country: United States
facility: Carl and Dorothy Bennett Cancer Center
state: Connecticut
city: Washington
country: United States
facility: VA Medical Center, Washington DC,
state: District of Columbia
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute - Emory University
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Salisbury
country: United States
facility: Peninsula Regional Cancer Center
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic-Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City VA Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Eastchester Center for Cancer Care
state: New York
city: Johnson City
country: United States
facility: Broome Oncology
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Mt Sinai Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College-NY Presbyterian Hospital
state: New York
city: Roslyn
country: United States
facility: St Francis Hospital
state: New York
city: Cary
country: United States
facility: Waverly Hematology Oncology
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Pinehurst
country: United States
facility: First Health Outpatient Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Tualatin
country: United States
facility: Northwest Cancer Specialists, PC
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwest Medical Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: Temple
country: United States
facility: Central Texas VA Healthcare Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Waco
country: United States
facility: Texas Oncology- Waco
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists PV
state: Virginia
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre, Alberta Health Services
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute, Alberta Health Services
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center, Royal Victoria Hospital
state: Quebec
city: Zaragoza
country: Spain
facility: Hospital Clinica Universitari Lozano Blesa
state: Aragón
city: Salamanca
country: Spain
facility: Hospital University de Salamanca
state: Castilla-León
city: Badalona
country: Spain
facility: H. U. Germans Trias i Pujol
state: Cataluña
city: Palma de Mallorca
country: Spain
facility: Hospital Univ Son Espases
state: Islas Baleares
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtze
state: Islas Baleares
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Quirón de Madrid
state: Madrid
city: San Sebastián de los Reyes
country: Spain
facility: University Hospital Infanta Sofia
state: Madrid
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
state: Navarra
city: Tenerife
country: Spain
facility: Hospital Universitari de Canarias
state: Santa Cruz
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
Study officials:
affiliation: Multiple Myeloma Research Foundation
name: Daniel Auclair
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.