Precision Medicine Study

Official title

Cancer Sequencing Guided Personalized and Precision Medicine Platform in Multiple Myeloma

Overview

This will be a 2 year study to evaluate and improve cancer sequencing as applied to the characterization of tumor molecular make-up and the identification of novel therapeutics (total n=100; approximately 50/year). Participants who will undergo tumor biopsy for management of multiple myeloma (MM) will self-refer to the study or be referred by their treating physician. Participants will initially meet with a clinician to review study consents and provide medical, medication, and family history information. After informed consent, biospecimen samples from peripheral blood, cheek swab, and tumor samples from bone marrow (aspirate and biopsy), peripheral blood, or any mass/fluid containing tumor cells will be obtained (from procedures indicated as part of their standard oncology care) for cancer sequencing (CS) (whole exome sequencing of germline and tumor genomes, RNA sequencing of tumor transcriptome, single cell, and CyTOF analysis). CS data will be interpreted via somatic variation identification, network modeling, and cancer transcriptome profiling to facilitate mapping activity levels of genes to networks and for identifying genes activated or dysregulated in cancer cells. Technologies and methodologies are developing rapidly, varying on a near daily basis which pre-empts our ability to define analysis and interpretation techniques in detail. Sequencing and analysis will be performed at the Genomics Core Facility at the Icahn School of Medicine at Mount Sinai. In instances where internal sequencing capabilities do not allow for certain types of analysis (e.g., a technology that is not yet available at Mount Sinai), de-identified samples or data may be sent out to third parties for additional analysis.. All external genetic tests will be performed in a CLIA certified lab and all tests will be FDA or NYS approved. The RNA Sequencing test will receive NYS Department of Health (Wadsworth Center) approval before results are provided to physicians . Samples will be de-identified and processed by the Mount Sinai Human Immune Monitoring Core (HIMC) before being sent to an external CLIA-certified lab for sequencing and analysis. Interpretation will be performed by a multidisciplinary team that includes genomicists, pathologists, and clinicians familiar with the particular cancer diagnosed in the participant. Once results are available, they will be shared with the study team. This study is not intended to implement the findings on CS, only to report the results obtained to the study team.

Primary outcome measures

• Total number of somatic Single-nucleotide variants (SNVs) per patient [Time frame: End of study at 30 months]

Secondary outcome measures (12)

• Total number of somatic insertions (INS) per patient [Time frame: End of study at 30 months]
• Total number of somatic deletions (DEL) per patient [Time frame: End of study at 30 months]
• Number of SNVs per megabase of the MM genome [Time frame: End of study at 30 months]
• Number of INS per megabase of the MM genome [Time frame: End of study at 30 months]
• Number of DEL per megabase of the MM genome [Time frame: End of study at 30 months]
• Number of mutations per megabase among MM subgroups [Time frame: End of study at 30 months]
• Number of mutations per megabase among genomic regions for all MM and mutational subgroups [Time frame: End of study at 30 months]
• Gene mutations identified [Time frame: End of study at 30 months]
• Chromosomal abnormalities identified [Time frame: End of study at 30 months]
• Molecular signatures identified [Time frame: End of study at 30 months]
• Established Prognostic markers identified [Time frame: End of study at 30 months]
• Somatic variants identified as targets of FDA-approved drugs (pharmacogenomics variant data) [Time frame: End of study at 30 months]

Eligibility criteria

Inclusion criteria

• Patients must be 18 years of age at the time of registration.
• Participant must have an established diagnosis of relapsed Multiple Myeloma based on IMWG criteria, be willing to participate, and able to consent
• Participant must have a treating physician who agrees to participate in the study
• Participant will be undergoing a bone marrow biopsy or tumor biopsy as part of their standard of care.
• Patients must be willing to participate in this study and able to sign informed consent.
• Participants are not participating in any interventional clinical trial using systemic therapy directed towards control of MM.

Exclusion criteria

• Known diagnosis of AL amyloidosis, Waldenstrom Macroglobulinemia, POEMS, or Castleman´s disease.
• Diagnosis of cancer other than myeloma or skin cancer (squamous cell or basal cell) that is ongoing or treated within the last 2 years.
• Tumor sample inadequate or unavailable for analysis (e.g., due to insufficient number of tumor cells).
• Patient will not be receiving systemic MM-directed chemotherapy/immunotherapy in the following 2 months from the time tumor biopsy is performed.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Mount Sinai Health System — New York

Identifiers

NCT: NCT06338150 · STUDY-23-00503 · GCO 19-0175 · 5R01CA244899

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗