Clinical trial NCT02726750: Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma
Official title: Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma (ORIGIN Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Monoclonal Gammopathy of Undetermined Significance
Smoldering Plasma Cell Myeloma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-04-04
Enrollment: 200
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: Patients with monoclonal gammopathy of unknown significance and/or smoldering multiple myeloma

Brief summary: The goal of this study is to find markers that may help to predict why some patients who have monoclonal gammopathy of unknown significance (MGUS) or smoldering multiple myeloma (SMM) that have no signs or symptoms of disease (asymptomatic) develop multiple myeloma, while others do not. Studying markers such as age, level of proteins in blood, percent of abnormal blood cells in the bone marrow, genes in the abnormal blood cells, and bone abnormalities may help researchers to validate clinical and genomic predictors for future use in clinical practice.

Detailed description: PRIMARY OBJECTIVE:

I. To determine the rate of progression to multiple myeloma after 3 years of follow up.

SECONDARY OBJECTIVES:

I. To describe baseline patient characteristics and clinical variables. II. To identify molecular and genetic correlates that may predict for progression to multiple myeloma (MM).

OUTLINE:

Patients undergo collection of blood samples every 6 months for 3 years. Patients may also undergo a biopsy, x-rays, positron emission tomography (PET)/computed tomography (CT) scans, and/or magnetic resonance imaging (MRI) scans to check the status of disease at the discretion of the treating physician.

After completion of 3 years on study, patients are followed up every 6-12 months thereafter.

Eligibility criteria: Inclusion Criteria:

* Patients with monoclonal gammopathy of unknown significance. Both criteria must be met:

  * Serum monoclonal protein \< 3 g/dL or urinary monoclonal protein \< 500 mg per 24 hours and clonal bone marrow plasma cells \< 10%
  * Absence of myeloma defining events or amyloidosis
* Patients with smoldering multiple myeloma. Both criteria must be met:

  * Serum monoclonal protein \>= 3 g/dL or urinary monoclonal protein \>= 500 mg per 24 hours and/or clonal bone marrow plasma cells 10-60%
  * Absence of myeloma defining events or amyloidosis

Exclusion Criteria:

* Evidence of myeloma defining events or biomarkers of malignancy due to underlying plasma cell proliferative disorder meeting at least one of the following

  * Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than the upper limit of normal or \> 2.75 mmol/L (\> 11 mg/dL)
  * Renal Insufficiency: creatinine clearance \< 40 ml/min or serum creatinine \> 2 mg/dL
  * Anemia: hemoglobin value \< 10 g/dL or 2 g/dL \< normal reference
  * Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2\[F-18\] fluoro-D-glucose positron emission tomography CT (PET-CT)
  * Clonal bone marrow plasma cell percentage \>= 60%
  * Involved:uninvolved serum free light chain ratio \>= 100 measured by Freelite assay (The Binding Site Group, Birmingham, United Kingdom \[UK\])
  * \> 1 focal lesions on magnetic resonance imaging (MRI) studies (each focal lesion must be 5 mm or more in size)
* Prior or concurrent systemic treatment for asymptomatic monoclonal gammopathies

  * Bisphosphonates are permitted
  * Radiotherapy is not permitted
  * Prior treatment with chemotherapy or investigational agents for asymptomatic gammopathies is not permitted
* Plasma cell leukemia
* Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements

Primary outcomes:
measure: Rate of progression to multiple myeloma (MM)
timeFrame: 3 years
measure: Progression free survival
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
Secondary outcomes:
measure: Baseline patient characteristics and clinical variables
timeFrame: Baseline
measure: Molecular and genetic profile analysis
timeFrame: 3 years
Other outcomes:
measure: Molecular profiling analysis of patients who develop MM
timeFrame: 3 years
measure: Immune characterization of patients who develop MM
timeFrame: 3 years
measure: Immune characterization of patients who develop MM
timeFrame: 3 years
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Krin Patel, MD
role: PRINCIPAL_INVESTIGATOR
References: