Two Biologically and Clinically Distinct Entities: Progressive Versus Stable Multiple Myeloma (MM) Precursor Conditions (TRANSFORMM)

Two Biologically and Clinically Distinct Entities: Progressive Versus Stable Multiple Myeloma (MM) Precursor Conditions (TRANSFORMM)

The key aim of the study is to define the two biologically and clinically distinct entities: progressive versus stable myeloma precursor conditions.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Carl Landgren, MD; Phone Number: 3052436578; Email: col15@miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Hospitals
      • Contact: Carl Landgren, MD; Phone Number: 305-243-6578; Email: col15@miami.edu
      • Principal Investigator: Carl Landgren, MD

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

Adult participants diagnosed with MGUS or SMM.

Description

Inclusion Criteria:

1. Diagnosis of MGUS and SMM will be made in accordance with the clinical diagnostic criteria set forth by the 2014 International Myeloma Working Group (IMWG) Revised Criteria.2
2. The diagnoses will be confirmed by either serum/urine protein electrophoresis, immunofixation and light-chain assays; or immunohistochemistry analyses of the bone marrow biopsy, or a combination of these tests.
3. Age greater than or equal to 18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
5. The patient must be competent to sign an informed consent form.

Exclusion Criteria:

1. A diagnosis of MM as defined as any patient with detectable M-protein in blood and/or urine, monoclonal plasma cells in the bone marrow, and evidence of end-organ damage based on the Calcium Elevation, Renal Failure, Anemia, and Bone Disease (CRAB) criteria and/or myeloma-defining events.

   • Patients who have received previous therapy for MM.
   • Patients with known plasma cell or related lymphoid (e.g. lymphoplasmacytic lymphoma, Amyloid Light chain (AL) amyloidosis)
2. Confirmation of pathological diagnosis is required either from the initial pathology review report or review from the UM/SCCC Hematopathologist in accordance with the clinical diagnostic criteria set forth by the International Myeloma Working Group (IMWG) or World Health Organization (WHO). Tumor tissue that has been previously collected and is available for study or that can be collected with minimal additional risk to the patient during sampling required for routine patient care or required testing on a University of Miami (UM) /Sylvester Comprehensive Cancer Center (SCCC) research protocol will be used for diagnosis.

3. Active symptomatic major organ disorder that would increase the risk of biopsy or other procedure, including but not limited to ischemic heart disease, recent myocardial infarction, active congestive heart failure, pulmonary dysfunction.

   • Active concomitant medical or psychological illnesses that may increase the risk to the patient or inability to obtain informed consent, at the discretion of the Principal Investigator.
   • Pregnant or breast-feeding women will not be eligible for any aspect of this protocol.
   • Prisoners will be excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Participants with MGUS or SMM; Participants with either Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM) will be followed for disease progression to active multiple myeloma (MM) for up to 5 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of progression to active Multiple Myeloma (MM)	The rate of progression to active multiple myeloma in participants with tumors with and without myeloma defining genomic events as evaluated by treating physician via clinical assessments (including low-input DNA whole-genome sequencing)	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of participant conversion from MGUS/SMM to Myeloma defining genomic events	As per treating physician evaluation of clinical assessments (including low-input DNA whole-genome sequencing)	Up to 5 years
Frequency of participant conversion from MGUS/SMM to associated progressive phenotype	As per treating physician evaluation of clinical assessments (including low-input DNA whole-genome sequencing)	Up to 5 years
Rate of participant conversion from MGUS/SMM to Myeloma defining genomic events	As per treating physician evaluation of clinical assessments (including low-input DNA whole-genome sequencing)	Up to 5 years
Rate of participant conversion from MGUS/SMM to associated progressive phenotype	As per treating physician evaluation of clinical assessments (including low-input DNA whole-genome sequencing)	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Carl Landgren, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: April 30, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• 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; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
• Other Study ID Numbers: 20220067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No