Smoldering Myeloma High-Risk Patient Observation and Longitudinal Insight Trial

NCT06212323 | Recruiting

• 1 other identifier: HCI170107
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to define the natural history of high-risk smoldering myeloma in a modern cohort of patients undergoing close standard of care follow-up with diffusion weighted whole body magnetic resonance imaging.

Conditions

Smoldering Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of morbid progression events attributable to a plasma cell dyscrasia at two years, with morbid events defined as: death, renal injury that does not reverse, fracture, lytic bone lesion, AL Amyloidosis or plasma cell leukemia.

  Frequency and nature of progression events in a prospective cohort of patients with smoldering myeloma undergoing active surveillance with diffusion weighted whole body MRI

  2 years

Secondary Outcomes (3)

• Change in the quality of life as measured by physical function domain on the PROMIS-29 (Patient-Reported Outcomes Measurement Information System), from baseline to the end of study at 24 months of follow-up.

  2 years

• Change in the quality of life as measured by pain interference domain on the PROMIS-29 (Patient-Reported Outcomes Measurement Information System), from baseline to the end of study at 24 months of follow-up.

  2 years

• Change in the quality of life as measured by anxiety domain on the PROMIS-29 (Patient-Reported Outcomes Measurement Information System), from baseline to the end of study at 24 months of follow-up.

  2 years

Interventions

Patients with smoldering myeloma undergoing active surveillance with diffusion weighted whole body MRI. OTHER

Patients with high-risk smoldering myeloma will be prospectively followed and chart review will be performed to determine if progression events happen, and how they happen. All patients on the study are recommended to undergo the following standard of care surveillance protocol: * Complete Blood Count (CBC), Complete Metabolic Panel (CMP), myeloma blood tests (serum kappa/lambda light chains, monoclonal protein evaluation, immunoglobulin levels), to be done monthly for first year, and then every two months for the second year. * WB DW-MRIs every 6 months during the study period. * 24-hour urine Immunofixation/electrophoresis is expected to be completed approximately every 6 months. * Bone marrow biopsy will be performed annually during the study time-period.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Smoldering myeloma (SMM)

You may qualify if:

• Adult subject aged ≥ 18 years.
• Diagnosis of smoldering myeloma as per the IMWG criteria, specifically:
• Serum monoclonal protein (IgG or IgA) of 30g/L or greater per 24 hours or urinary monoclonal protein of 500mg or greater per 24 hours and/or
• Clonal bone marrow plasma cells 10-59% with the absence of myeloma-defining events or amyloidosis
• High-risk smoldering myeloma defined as two or more out of four of the following criteria:
• M-spike greater than 2 g/dL
• An involved/uninvolved free light chain ratio greater than 20
• Bone marrow plasmacytosis greater than 20%
• Presence of any of translocation (4;14), deletion 17p, deletion 13q or 1q gain by conventional cytogenetics/fluorescence in situ hybridization (FISH) studies) and/or
• An IMWG SMM score of 9 or greater according to the IMWG risk model for smoldering multiple myeloma (SMM)
• Diagnosis of high-risk SMM made within 365 days of enrollment in the study. Note: If a patient previously had MGUS or low/intermediate SMM- the date at which high-risk SMM was diagnosed would have to be within 365 days of enrollment in the study.

You may not qualify if:

• Presence of any features that would meet diagnostic criteria for myeloma as per the IMWG Criteria
• Presence of extramedullary plasmacytomas
• Creatinine clearance of less than 40ml/min.
• Presence of AL Amyloidosis (the amount of workup necessary to exclude AL Amyloidosis is per the discretion of the treating investigator, however the investigator must attest that they do not believe AL Amyloidosis to be present at time of enrollment. Serum nt-PROBNP is recommended as part of evaluation in order to ascertain for cardiac amyloidosis).
• Note: The Hgb cut-offs can vary between institutions (lower cut-off for Hgb University of Utah for men is a Hgb of 14.8, rendering a patient with Hgb of 12.7 as having a CRAB feature). If the Hgb is above 10g/dl but the patient meets the definition of anemia according to the IMWG criteria, by virtue of this being more than 2 g/dl below the limit of normal, the investigator can decide whether to call a patient being considered for screening as having multiple myeloma OR smoldering myeloma and allow enrollment on this study.
• Given that the values used to define high-risk SMM can change, at time of enrollment, if utilizing at least 2/4 of the 2/20/20+cytogenetics criteria to enroll, participants should meet at least 2/4 of the 2/20/20. If participants had met at least 2/4 previously at some timepoint but do not meet at least 2/4 currently, they cannot be enrolled in the study.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute at the University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Related Publications (17)

• Cowan A, Ferrari F, Freeman SS, et al: Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study. Lancet Haematol 10:e203-e212, 2023

  BACKGROUND

• Mateos MV, Kumar S, Dimopoulos MA, et al: International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J 10:102, 2020

  BACKGROUND

• Lakshman A, Rajkumar SV, Buadi FK, et al: Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J 8:59, 2018

  BACKGROUND

• Rajkumar SV, Dimopoulos MA, Palumbo A, et al: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538-48, 2014

  BACKGROUND

• Thorsteinsdottir S, Gislason GK, Aspelund T, et al: Prevalence of smoldering multiple myeloma based on nationwide screening. Nat Med 29:467-472, 2023

  BACKGROUND

• Hillengass J, Moulopoulos LA, Delorme S, et al: Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group. Blood Cancer J 7:e599, 2017

  BACKGROUND

• Siontis B, Kumar S, Dispenzieri A, et al: Positron emission tomography- computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy. Blood Cancer J 5:e364, 201

  BACKGROUND

• Perez-Persona E, Vidriales MB, Mateo G, et al: New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 110:2586-92, 2007

  BACKGROUND

• Dispenzieri A, Kyle RA, Katzmann JA, et al: Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 111:785-9, 2008

  BACKGROUND

• Hill E, Dew A, Morrison C, et al: Assessment of Discordance Among Smoldering Multiple Myeloma Risk Models. JAMA Oncol 7:132-134, 2021

  BACKGROUND

• Lonial S, Jacobus S, Fonseca R, et al: Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma. J Clin Oncol 38:1126-1137, 2020

  BACKGROUND

• Mateos MV, Hernandez MT, Giraldo P, et al: Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 369:438-47, 2013

  BACKGROUND

• Mateos MV, Hernandez MT, Salvador C, et al: Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study. Eur J Cancer 174:243-250, 2022

  BACKGROUND

• Wennmann M, Goldschmidt H, Mosebach J, et al: Whole-body magnetic resonance imaging plus serological follow-up for early identification of progression in smouldering myeloma patients to prevent development of end-organ damage. Br J Haematol 199:65-75, 2022

  BACKGROUND

• Hays RD, Spritzer KL, Schalet BD, et al: PROMIS((R))-29 v2.0 profile physical and mental health summary scores. Qual Life Res 27:1885-1891, 2018

  BACKGROUND

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 BACKGROUND

• Hays RD, Spritzer KL, Schalet BD, et al: PROMIS(®)-29 v2.0 profile physical and mental health summary scores. Qual Life Res 27:1885-1891, 2018

  BACKGROUND

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ghulam Rehman Mohyuddin, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sharmilee Nuli

CONTACT

801-585-0255; Sharmilee.Nuli@hci.utah.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 18, 2024
• Study Start: January 11, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)