Clinical trial NCT00639054: The Molecular Characterization of Multiple Myeloma at Relapse
Official title: The Molecular Characterization of Multiple Myeloma at Relapse
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Myeloma
Keywords: classification
diagnosis
genetics
mortality
pathology
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Herlev Hospital
name: Zealand University Hospital
name: Naestved Hospital
name: Agnes og Poul Friis Fond
name: Carl og Ellen Hertzs Legat til Dansk Læge- og Naturvidenskab
name: Dagmar Marshalls Fond
name: Danish Cancer Research Foundation
name: Direktør Jacob Madsen og hustru Olga Madsens Fond
name: Elna og Jørgen Fagerholt Pedersens Kræftforskningsfond
name: Eva og Henry Frænkels Mindefond
name: Manufacturer Einar Willumsen's memorial team
name: Fonden til Lægevidenskabens Fremme
name: Grosserer M. Brogaard og Hustrus Mindefond
name: Højmosegård-Legatet
name: Janssen-Cilag, S.A.
name: Karen A. Tolstrups fond
name: Krista og Viggo Petersens Fond
name: Købmand Sven Hansen og hustru Ina Hansens Fond
name: Meta og Håkon Baggers Fond
name: Reinholdt W. Jorck og hustrus Fond
First posted: 2008-03-19
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed and/or treated at departments of hematology. Healthy controls.

Brief summary: Observational study investigating prognostic factors in newly diagnosed and relapsed multiple myeloma patients by use of clinical data, biochemical markers (blood samples), cytogenetic markers and gene expression profiling (myeloma cells from fresh bone marrow samples). Enabling future genetic studies by establishing a biobank of bone marrow and peripheral blood samples.

Detailed description: Multiple myeloma (MM) is an incurable cancer. The disease can often be brought to a halt with chemotherapy which in younger patients is accompanied by stem cell transplantation. But the disease relapses almost invariably. Cytogenetic changes in the myeloma cells can serve as prognostic markers. Accordingly, 25% of the patients show changes associated with a prognosis so poor that they should probably receive experimental treatment right from the start. Nevertheless, a part of these patients survive much longer than expected. Thus, the prognosis must depend on additional genetic events.

The aim of this project is to widen the investigators knowledge of the nature, chronology and prognostic value of the genetic events in MM in order to improve the risk stratification of the patients and hence the choice of treatment. Using cytogenetics (interphase FISH) and molecular biological analyses (SNP, GEP, miRNA) the investigators will study the changes in the myeloma cells. The investigators will search for genetic and clinical differences between patients within the same cytogenetic group and between patients at diagnosis and at relapse. The study population will consist of 100 newly diagnosed patients and 100 relapse patients included prospectively over a 2-year period in a cooperation between the four departments of hematology in Zealand, Denmark.

Hypotheses:

1. Early relapse depends on a) molecular defects in the myeloma cells detectable with FISH, GEP, SNP and/or miRNA analyses, and b) the acquisition of new mutations resulting in chemotherapy resistance and increased prolific capacity.
2. The progressive reduction of event free survival seen with every relapse until the disease turns refractory can be explained by selection of critical mutations.
3. The cytogenetic changes associated with poor prognosis represent a heterogenous group of patients in whom the responsible genetic events remain unknown.

Eligibility criteria: Inclusion Criteria:

* patients newly diagnosed with multiple myeloma and at the same time eligible for high dose chemotherapy and autologous stem cell transplantation
* patients with multiple myeloma experiencing relapse after high dose chemotherapy and autologous stem cell transplantation

Exclusion Criteria:

* for newly diagnosed patients: age or comorbidity preventing high dose chemotherapy and autologous stem cell transplantation,
* for all patients: age below 18, physical or psychological incapability to give an informed consent.

Primary outcomes:
measure: Molecular characteristics (by FISH, SNP, GEP, miRNA)
timeFrame: 0-3 years
Secondary outcomes:
measure: Event free survival (EFS)
timeFrame: 0-10 years
measure: Overall survival (OS)
timeFrame: 0-10 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Multiple Myeloma Research Laboratory, Dept Hematology, Cph Univ Hosp Rigshospitalet
state: Capital Region
Study officials:
affiliation: Rigshospitalet, Denmark
name: N Emil U Hermansen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Peter Gimsing, MD, DMSc
role: STUDY_CHAIR
affiliation: Zealand University Hospital
name: Annette J Vangsted, MD, DMSc
role: STUDY_CHAIR
affiliation: Rigshospitalet, Denmark
name: Mette K Andersen, MD, DMSc
role: STUDY_CHAIR
affiliation: Rigshospitalet, Denmark
name: Finn C Nielsen, MD, DMSc
role: STUDY_CHAIR
affiliation: Naestved Hospital, Denmark
name: Dan Kristensen, MD
role: STUDY_CHAIR
affiliation: Herlev Hospital
name: Nielsaage T Clausen, MD
role: STUDY_CHAIR
References:
citation: Hermansen NE, Borup R, Andersen MK, Vangsted AJ, Clausen NT, Kristensen DL, Nielsen FC, Gimsing P. Gene expression risk signatures maintain prognostic power in multiple myeloma despite microarray probe set translation. Int J Lab Hematol. 2016 Jun;38(3):298-307. doi: 10.1111/ijlh.12486. Epub 2016 Mar 29.