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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Multiple Myeloma

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Newly diagnosed Multiple Myeloma<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloma, Multiple Myeloma, Observational, Longitudinal