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

This study has been completed.
Sponsor:
Collaborators:
Herlev Hospital
Roskilde County Hospital
Naestved Hospital
Agnes og Poul Friis Fond
Carl og Ellen Hertzs Legat til Dansk Læge- og Naturvidenskab
Dagmar Marshalls Fond
Danish Cancer Research Foundation
Direktør Jacob Madsen og hustru Olga Madsens Fond
Elna og Jørgen Fagerholt Pedersens Kræftforskningsfond
Eva og Henry Frænkels Mindefond
Fabrikant Einar Willumsens Mindelegat
Fonden til Lægevidenskabens Fremme
Grosserer M. Brogaard og Hustrus Mindefond
Højmosegård-Legatet
Janssen-Cilag, S.A.
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
Information provided by (Responsible Party):
N. Emil U. Hermansen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00639054
First received: March 11, 2008
Last updated: January 6, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention
Multiple Myeloma
Procedure: Bone marrow examination
Procedure: Blood samples

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Molecular Characterization of Multiple Myeloma at Relapse

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Molecular characteristics (by FISH, SNP, GEP, miRNA) [ Time Frame: 0-3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Event free survival (EFS) [ Time Frame: 0-10 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 0-10 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
Peripheral whole blood Bone marrow

Enrollment: 134
Study Start Date: March 2008
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients diagnosed and/or treated at departments of hematology. Healthy controls.
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00639054

Locations
Denmark
Multiple Myeloma Research Laboratory, Dept Hematology, Cph Univ Hosp Rigshospitalet
Copenhagen, Capital Region, Denmark, DK-2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Herlev Hospital
Roskilde County Hospital
Naestved Hospital
Agnes og Poul Friis Fond
Carl og Ellen Hertzs Legat til Dansk Læge- og Naturvidenskab
Dagmar Marshalls Fond
Danish Cancer Research Foundation
Direktør Jacob Madsen og hustru Olga Madsens Fond
Elna og Jørgen Fagerholt Pedersens Kræftforskningsfond
Eva og Henry Frænkels Mindefond
Fabrikant Einar Willumsens Mindelegat
Fonden til Lægevidenskabens Fremme
Grosserer M. Brogaard og Hustrus Mindefond
Højmosegård-Legatet
Janssen-Cilag, S.A.
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 Roskilde County 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
  More Information

Responsible Party: N. Emil U. Hermansen, Ph.D student, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT00639054     History of Changes
Other Study ID Numbers: 959593931/Emil Hermansen  H-B-2007-117 
Study First Received: March 11, 2008
Last Updated: January 6, 2016
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: National Board of Health
Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by Rigshospitalet, Denmark:
classification
diagnosis
genetics
mortality
pathology

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 28, 2016