Clinical trial NCT06338150: Precision Medicine Study
Official title: Cancer Sequencing Guided Personalized and Precision Medicine Platform in Multiple Myeloma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Myeloma
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-03-29
Enrollment: 100
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: This study is open to interested patients with Multiple Myeloma (MM) of all genders and races from inside or outside Mount Sinai that will be undergoing tumor sampling (bone marrow or tissue) as part of their evaluation for salvage therapy. The research team will accept participants with a diagnosis of MM who self-refer, or are referred by their treating physician, who will be undergoing tumor biopsy (bone marrow or tissue) with the intention of receiving salvage systemic therapy for their MM. Interested individuals can contact the research team and learn more about the study. Potential participants would speak to one of the study staff over the phone, will be provided with further details about the study, pre-screened for eligibility, and set up to undergo informed consent.

Brief summary: 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 (n=100). 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. 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, de-identified samples or data may be sent out to third parties for additional analysis. The study will be using GenPath, a division of BioReference® Health, LLC for this project which is a CLIA certified lab. All 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 and patients. 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 participant and treating physician during a follow-up results session and any findings obtained explained. This study is not intended to implement findings, only to report them.


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.

Primary outcomes:
measure: Total number of somatic Single-nucleotide variants (SNVs) per patient
timeFrame: End of study at 30 months
Secondary outcomes:
measure: Total number of somatic insertions (INS) per patient
timeFrame: End of study at 30 months
measure: Total number of somatic deletions (DEL) per patient
timeFrame: End of study at 30 months
measure: Number of SNVs per megabase of the MM genome
timeFrame: End of study at 30 months
measure: Number of INS per megabase of the MM genome
timeFrame: End of study at 30 months
measure: Number of DEL per megabase of the MM genome
timeFrame: End of study at 30 months
measure: Number of mutations per megabase among MM subgroups
timeFrame: End of study at 30 months
measure: Number of mutations per megabase among genomic regions for all MM and mutational subgroups
timeFrame: End of study at 30 months
measure: Gene mutations identified
timeFrame: End of study at 30 months
measure: Chromosomal abnormalities identified
timeFrame: End of study at 30 months
measure: Molecular signatures identified
timeFrame: End of study at 30 months
measure: Established Prognostic markers identified
timeFrame: End of study at 30 months
measure: Somatic variants identified as targets of FDA-approved drugs (pharmacogenomics variant data)
timeFrame: End of study at 30 months
measure: Network-informed key driver variants identified
timeFrame: End of study at 30 months
measure: Transcriptome variations identified
timeFrame: End of study at 30 months
measure: Germline mutations identified in cancer predisposition genes
timeFrame: End of study at 30 months
measure: FDA approved drugs available that block enzymes produced in those pathways identified
timeFrame: End of study at 30 months
measure: Treatment recommended by computational pipeline based on patient's clinical and genetic
timeFrame: End of study at 30 months
measure: Germline whole exome sequencing profile
timeFrame: End of study at 30 months
measure: Tumor genome whole exome sequencing profile
timeFrame: End of study at 30 months
measure: Tumor transcriptome profile
timeFrame: End of study at 30 months
measure: Single-cell sequencing profile
timeFrame: End of study at 30 months
measure: Cytometric profile
timeFrame: End of study at 30 months
measure: Signaling Pathways associated
timeFrame: End of study at 30 months
measure: Enzymes associated with each signaling pathway identified
timeFrame: End of study at 30 months
measure: Improvement of cancer sequencing-guided treatment recommendations by machine learning
timeFrame: End of study at 30 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Health System
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Cesar Rodriguez Valdes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: