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

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Completed

CT.gov ID

NCT00639054

Collaborator

Herlev Hospital (Other), Zealand University Hospital (Other), Naestved Hospital (Other), Agnes og Poul Friis Fond (Other), Carl og Ellen Hertzs Legat til Dansk Læge- og Naturvidenskab (Other), Dagmar Marshalls Fond (Other), Danish Cancer Research Foundation (Other), Direktør Jacob Madsen og hustru Olga Madsens Fond (Other), Elna og Jørgen Fagerholt Pedersens Kræftforskningsfond (Other), Eva og Henry Frænkels Mindefond (Other), Manufacturer Einar Willumsen's memorial team (Other), Fonden til Lægevidenskabens Fremme (Other), Grosserer M. Brogaard og Hustrus Mindefond (Other), Højmosegård-Legatet (Other), Janssen-Cilag, S.A. (Industry), Karen A. Tolstrups fond (Other), Krista og Viggo Petersens Fond (Other), Købmand Sven Hansen og hustru Ina Hansens Fond (Other), Meta og Håkon Baggers Fond (Other), Reinholdt W. Jorck og hustrus Fond (Other)

134

Enrollment

Location

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	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:

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.
The progressive reduction of event free survival seen with every relapse until the disease turns refractory can be explained by selection of critical mutations.
The cytogenetic changes associated with poor prognosis represent a heterogenous group of patients in whom the responsible genetic events remain unknown.

Study Design

Study Type:

Observational

Actual Enrollment :

134 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Molecular Characterization of Multiple Myeloma at Relapse

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

Molecular characteristics (by FISH, SNP, GEP, miRNA) [0-3 years]

Secondary Outcome Measures

Event free survival (EFS) [0-10 years]
Overall survival (OS) [0-10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.