Clinical trial NCT03327597: Iceland Screens, Treats or Prevents Multiple Myeloma
Official title: Iceland Screens, Treats or Prevents Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Monoclonal Gammopathy of Undetermined Significance
Keywords: MGUS
Screening
Population-based
Lead sponsor: University of Iceland
Sponsor class: OTHER
Collaborators: name: Landspitali University Hospital
name: Union for International Cancer Control
name: Icelandic Heart Association
name: deCODE genetics
name: International Myeloma Foundation/Black Swan Research Initiative
name: The Binding Site
name: Memorial Sloan Kettering Cancer Center
name: European Research Council
name: The Icelandic Centre for Research
First posted: 2017-10-31
Enrollment: 80761
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: This study will assess the benefits and harms of screening for monoclonal gammopathy of undetermined significance (MGUS). The overall and disease-specific mortality will be compared between screened and not screened participants. All individuals registered as inhabitants in Iceland and born in 1975 or earlier have been invited to participate. The hypothesis is that an early detection of multiple myeloma (MM), through follow-up of MGUS, will improve overall survival and decrease complications associated with diagnosis and treatment of MM.

Detailed description: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant stage that almost always precedes multiple myeloma (MM) and amyloidosis. It is defined by a monoclonal-(M)-protein detected on serum protein electrophoresis or immunofixation electrophoresis and can be diagnosed with a blood sample. Approximately four percent of individuals 50 years or older have MGUS which is associated with a 1-2% annual risk of malignant transformation but it is impossible to predict which individuals diagnosed as having MGUS will progress and receive a diagnosis of malignant disease.

To date, no evidence is available on the benefits and harms of population-based screening for MGUS and data from prospective studies that assess the optimal follow-up of MGUS are lacking.

All individuals that are registered as inhabitants in Iceland and born in 1975 or earlier have been invited to participate in the study. After signing informed consent, serum from the participants will be analysed for MGUS. The participants will not be contacted for blood sampling. Instead, an innovative approach will be used by taking advantage of the fact that most people 40 years or older do a blood test for various reasons during a three year period. The ID-list of participants in the study will be cross-linked with all major laboratories in Iceland, covering approximately 90% of all blood sampling in Iceland. When a participant has a blood test, a small amount (1 ml) of serum will be sampled and put in a separate test tube belonging to the study and used for diagnosis of MGUS.

Participants diagnosed as having MGUS will be randomized to three different arms, of which two arms will be called into a clinical study center for two separate types of follow-up. In arm one the participants will be asked to answer an electronic Mental Health and Quality of Life questionnaire annually but receive no active follow-up. In arm two and three the participants will be asked to answer the Mental Health and QoL questionnaire but also receive follow-up according to the International Myeloma Working Group (IMWG) guidelines (arm two) or intensive (arm three) clinical follow-up. Participants without MGUS will be asked to answer Mental Health and QoL questionnaire annually.

Results from two recent, population-based studies shows that early detection of MM through follow-up of MGUS is associated with fewer major complications and 13-14% better overall survival as compared to individuals presenting with MM without previous diagnosis of MGUS.

This study aims to assess the benefits and harms of population-based screening for MGUS by analyzing overall and disease specific survival, complications associated with screening and the effects screening has on mental health and quality of life. Furthermore, the aim of the study is to evaluate the optimal follow-up strategy of MGUS and the cost-effectiveness of screening for MGUS.

Eligibility criteria: Inclusion Criteria:

* Born 1975 or earlier
* With registered address in Iceland on November 1st 2016

Exclusion Criteria:

* Prior multiple myeloma
* Lymphoproliferative disease
* Amyloidosis
* M-protein \>30 g/L or involved:uninvolved serum FLC ratio \>100

Individuals with prior history of MGUS will be offered to be randomized into either moderate or intensive clinical follow-up (arms 2 or 3).

Primary outcomes:
measure: Overall survival
timeFrame: 5 years from study start.
Secondary outcomes:
measure: Cause specific survival
timeFrame: 5 years from study start
measure: Cost-effectiveness of screening for MGUS
timeFrame: 5 years from study start
measure: Global satisfaction with one´s life as assessed by the Satisfaction with life (SWLS)
timeFrame: 5 years from study start.
measure: Happiness as assessed by the Single item measure for happiness
timeFrame: 5 years from study start
measure: Resilience as assessed by The Connor-Davidson resilience scale (CD-RISC)
timeFrame: 5 years from study start
measure: Social support as assessed by the Multidimensional scale of perceived social support (MSPSS)
timeFrame: 5 years from study start
measure: Adverse childhood experiences as assessed by the Adverse childhood experiences international questionnaire (ACE-IQ)
timeFrame: 5 years from study start
measure: Depressive symptoms as assessed by the Patient health questionnaire (PHQ-9)
timeFrame: 5 years from study start
measure: Anxiety symptoms as assessed by the Generalized anxiety disorder (GAD-7)
timeFrame: 5 years from study start
measure: Worry as assessed by the Single item measure for worry
timeFrame: 5 years from study start
measure: Stress as assessed by the Perceived stress scale (PSS-10)
timeFrame: 5 years from study start
measure: Post-traumatic stress symptoms as assessed by the Posttraumatic stress disorder checklist for DMS-5 (PCL-5) including the Life Events Checklist for DSM-5 (LEC-5)
timeFrame: 5 years from study start
measure: Health as assessed by the 36-Item short form survey (SF-36)
timeFrame: 5 years from study start
Other outcomes:
Locations:
city: Reykjavík
country: Iceland
facility: University of Iceland
Study officials:
affiliation: University of Iceland
name: Sigurdur Y Kristinsson, Professor
role: PRINCIPAL_INVESTIGATOR
References: