Pharmacogenomic Study in Myeloma Patients Treated With Melphalan-prednisone-thalidomide or Lenalidomide-dexamethasone

Myeloma Clinical Trial

Official title:

Pharmacogenomic Study to Predict Survival, Best Response and Toxicity in Newly Diagnosed Myeloma Patients Above the Age of 65 Treated With Either a Combination of Melphalan-prednisone-thalidomide or Lenalidomide-dexamethasone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00907452
• Other study ID #: IFM 2007-03
• Secondary ID: Eudract: 2008-00
• Status: Completed
• Phase: N/A
• Start date: July 29, 2009
• Est. completion date: July 14, 2016

Study information

• Verified date: March 2021
• Source: Intergroupe Francophone du Myelome
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This protocol (in patients aged 65 and over suffering from previously untreated multiple myeloma), represents the first worldwide, pharmacogenomic study on this scale in terms of the number of patients analyzed and the implemented molecular diagnostics resources. The goal is to be able to identify patients who will best respond to the study treatments or experience the fewest associated side effects and improve prognosis, in order to optimize care management in multiple myeloma. To this end, the study seeks to predict the following parameters in these patients: - The treatment response and occurrence of adverse events linked to a lenalidomide-dexamethasone combination or a melphalan-prednisone-thalidomide combination. - Progression-free survival and overall survival. Prediction of the treatment response and the occurrence of adverse effects will be based on: - An analysis of constitutive genetic traits linked to single nucleotide polymorphisms and DNA copy number variations. - An analysis of changes in the tumor's genotype (change in the DNA copy number) and phenotype (altered gene and micro-RNA expression). Prediction of progression-free survival and overall survival will be based on an analysis of changes in the tumor's genotype and phenotype.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: July 14, 2016
• Est. primary completion date: December 14, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form
• Age = 65 years at the time of signing consent
• Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:

MM diagnostic criteria (all 3 required)

• Monoclonal plasma cells in the bone marrow =10% and/or presence of a biopsy-proven plasmacytoma
• Monoclonal protein present in the serum and/or urine
• Myeloma-related organ dysfunction (at least one of the following):
• Calcium elevation in the blood (serum calcium > 10.5 mg/l or upper limit of normal)
• Renal insufficiency (serum creatinine > 2 mg/dl)
• Anemia (hemoglobin < 10 g/dl or 2 g < normal)
• Lytic bone lesions or osteoporosis
• have measurable disease by protein electrophoresis analyses as defined by the

following:

• IgG multiple myeloma: Serum monoclonal paraprotein (M-protein)level = 1.0 g/dL or urine M-protein level = 200 mg/24 h
• IgA multiple myeloma: Serum M-protein level ³ 0.5 mg/dL or urine M-protein level³ 200 mg/24 h
• IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level = 1.0 g/dL or urine Mprotein level = 200 mg/24h
• IgD multiple myeloma: Serum M-protein level = 0.05 g/dL or urine M-protein level = 200 mg/24h
• Light chain multiple myeloma: Serum M-protein level = 1.0 g/dL or urine Mprotein level = 200 mg/24 hours
• ECOG performance status of 0, 1, or 2
• Treated by either melphalan-prednisone-thalidomide or lenalidomide- dexamethasone

Exclusion Criteria:

• Previous treatment with antimyeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 28 days (4 weeks) of randomization]
• Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study
• Any of the following laboratory abnormalities :
• Absolute neutrophil count (ANC) < 1,000 cells/µL (1.0 x 109/L)
• Platelet count < 50,000 cells/µL (50 x 109/L) for patients in whom < 50% of bone marrow nucleated cells are plasma cells; but platelet count < 30,000/µL for patients in whom = 50% of bone marrow nucleated cells are plasma cells
• Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)
• Creatinine clearance = 30 mL/min (Cockroft-Gault calculation)
• Prior history of malignancies, other than multiple myeloma, unless the subject has

been free of the disease for = 3 years. Exceptions include the following:

• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
• Patients who have are unable or unwilling to undergo antithrombotic therapy
• Peripheral neuropathy of > grade 2 severity
• Known HIV positivity or active infectious hepatitis, type A, B, or C.
• Primary AL amyloidosis and myeloma complicated by amyloidosis.
• Renal failure requiring dialysis

Related Conditions & MeSH terms

• Multiple Myeloma
• Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• melphalan-prednisone-thalidomide

• lenalidomide-dexamethasone

Locations

Country	Name	City	State
France	CH ALBI	Albi
France	CHRU Angers	Angers
France	CH Côte basque	Bayonne
France	CH Blois	Blois
France	BORDEAUX	Bordeaux
France	Chalon sur Saone	Chalon-sur-Saône
France	CHU Dijon	Dijon
France	Ch Dunkerque	Dunkerque
France	Chu Grenoble	Grenoble
France	CHD Vendée	La Roche Sur Yon
France	CHRU Lille	Lille
France	CHU LYON	Lyon
France	LYON SUD	Lyon
France	Ipc Marseille	Marseille
France	CHR METZ	Metz
France	CH Mulhouse	Mulhouse
France	Chu Nancy	Nancy
France	Chu Nantes	Nantes
France	Centre Antoine LACASSAGNE	Nice
France	Institut Curie	Paris
France	Chu Poitiers	Poitiers
France	Chu Rennes	Rennes
France	CH Yves Le Foll	St Brieuc
France	René Huguenin	St CLOUD
France	Chu Toulouse	Toulouse
France	Chu Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Intergroupe Francophone du Myelome

Country where clinical trial is conducted

France, 

References & Publications (1)

Miannay B, Minvielle S, Roux O, Drouin P, Avet-Loiseau H, Guérin-Charbonnel C, Gouraud W, Attal M, Facon T, Munshi NC, Moreau P, Campion L, Magrangeas F, Guziolowski C. Logic programming reveals alteration of key transcription factors in multiple myeloma. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	best response to treatment	best response rate	1 year