Clinical trial NCT06212323: Smoldering Myeloma High-Risk Patient Observation and Longitudinal Insight Trial
Official title: Smoldering Myeloma High-Risk Patient Observation and Longitudinal Insight Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Smoldering Multiple Myeloma
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2024-01-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Smoldering myeloma (SMM)

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Presence of any features that would meet diagnostic criteria for myeloma as per the IMWG Criteria
* Presence of extramedullary plasmacytomas
* Presence of any focal bone marrow lesions, or lytic bone lesions on imaging done prior to screening or on screening. However, presence of diffuse or patchy infiltration of the marrow (without any clear lesions) on MRI, will not be an exclusion criteria. Patients with 1 focal marrow lesion on MRI that is attributable to plasma cell dyscrasia, will be excluded from study, even if they do not meet criteria for myeloma.
* 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).
* Hemoglobin of less than 11g/dl, unless a clearly reversible reason for anemia is identified, at which point they can be rescreened in two months if Hgb is greater than 11g/dl.

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.

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at the University of Utah
state: Utah
Study officials:
affiliation: Huntsman Cancer Institute
name: Ghulam Rehman Mohyuddin, MD
role: PRINCIPAL_INVESTIGATOR
References: