The Molecular Characterization of Multiple Myeloma at Relapse (MM-FISH/DNA)

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Procedure: Bone marrow examination; Procedure: 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.

• Study Type: Observational
• Enrollment (Actual): 134

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Copenhagen, Capital Region, Denmark, DK-2100
      • Multiple Myeloma Research Laboratory, Dept Hematology, Cph Univ Hosp Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed and/or treated at departments of hematology. Healthy controls.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Newly diagnosed patients; Newly diagnosed high-dose therapy candidates. Participation means bone marrow examination (donating 7.5 ml of fresh bone marrow) and blood samples (24 ml of peripheral blood) for biochemical and genetic analyses regarding multiple myeloma, and granting access to clinical data relating to multiple myeloma.	Procedure: Bone marrow examination; 7.5 ml of iliac crest bone marrow drawn in addition to diagnostic samples.; Procedure: Blood samples; 24 ml of cubital vein blood drawn in addition to diagnostic samples.
Relapse patients; Formerly high-dose treated patients with progressive disease. Participation means bone marrow examination (donating 7.5 ml of fresh bone marrow) and blood samples (24 ml of peripheral blood) for biochemical and genetic analyses regarding multiple myeloma, and granting access to clinical data relating to multiple myeloma.	Procedure: Bone marrow examination; 7.5 ml of iliac crest bone marrow drawn in addition to diagnostic samples.; Procedure: Blood samples; 24 ml of cubital vein blood drawn in addition to diagnostic samples.
Healthy controls; Healthy blood and bone marrow donors. Participation means bone marrow examination (donating 7.5 ml of fresh bone marrow) for genetic analyses serving to compare normal bone marrow with bone marrow from multiple myeloma patients.	Procedure: Bone marrow examination; 7.5 ml of iliac crest bone marrow drawn in addition to diagnostic samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Molecular characteristics (by FISH, SNP, GEP, miRNA)	0-3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Event free survival (EFS)	0-10 years
Overall survival (OS)	0-10 years

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Zealand University Hospital; Herlev Hospital; Fonden til Lægevidenskabens Fremme; Naestved Hospital; Janssen-Cilag, S.A.; Eva og Henry Frænkels Mindefond; Dagmar Marshalls Fond; Danish Cancer Research Foundation; Agnes og Poul Friis Fond; Carl og Ellen Hertzs Legat til Dansk Læge- og Naturvidenskab; Direktør Jacob Madsen og hustru Olga Madsens Fond; Elna og Jørgen Fagerholt Pedersens Kræftforskningsfond; Manufacturer Einar Willumsen's memorial team; Grosserer M. Brogaard og Hustrus Mindefond; Højmosegård-Legatet; Karen A. Tolstrups fond; Krista og Viggo Petersens Fond; Købmand Sven Hansen og hustru Ina Hansens Fond; Meta og Håkon Baggers Fond; Reinholdt W. Jorck og hustrus Fond
• Investigators: Principal Investigator: N Emil U Hermansen, MD, Rigshospitalet, Denmark; Study Chair: Peter Gimsing, MD, DMSc, Rigshospitalet, Denmark; Study Chair: Annette J Vangsted, MD, DMSc, Zealand University Hospital; Study Chair: Mette K Andersen, MD, DMSc, Rigshospitalet, Denmark; Study Chair: Finn C Nielsen, MD, DMSc, Rigshospitalet, Denmark; Study Chair: Dan Kristensen, MD, Naestved Hospital, Denmark; Study Chair: Nielsaage T Clausen, MD, Herlev Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 11, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (Estimate): March 19, 2008

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: genetics; mortality; diagnosis; classification; pathology
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 959593931/Emil Hermansen; H-B-2007-117 (Other Identifier: The National Committee on Health Research Ethics (Denmark))