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

NCT00907452 | Completed

• 2 other identifiers: IFM 2007-03Eudract: 2008-003486-58
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 26

Brief 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.

Conditions

Myeloma

Keywords

Pharmacogenomics; prediction response; prediction adverse event

Outcome Measures

Primary Outcomes (1)

• best response to treatment

  best response rate

  1 year

Study Arms (2)

melphalan-prednisone-thalidomide

ACTIVE COMPARATOR

Drug: melphalan-prednisone-thalidomide

lenalidomide-dexamethasone

ACTIVE COMPARATOR

Drug: lenalidomide-dexamethasone

Interventions

melphalan-prednisone-thalidomide DRUG

melphalan-prednisone-thalidomide

lenalidomide-dexamethasone DRUG

lenalidomide-dexamethasone

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Intergroupe Francophone du Myelome: lead

Study Sites (26)

CH ALBI

Albi, France

Location

CHRU Angers

Angers, France

Location

CH Côte basque

Bayonne, France

Location

CH Blois

Blois, France

Location

BORDEAUX

Bordeaux, France

Location

Chalon sur Saone

Chalon-sur-Saône, France

Location

CHU Dijon

Dijon, France

Location

Ch Dunkerque

Dunkirk, France

Location

Chu Grenoble

Grenoble, France

Location

CHD Vendée

La Roche-sur-Yon, France

Location

CHRU Lille

Lille, France

Location

CHU LYON

Lyon, France

Location

LYON SUD

Lyon, France

Location

Ipc Marseille

Marseille, France

Location

CHR METZ

Metz, France

Location

CH Mulhouse

Mulhouse, France

Location

Chu Nancy

Nancy, France

Location

Chu Nantes

Nantes, France

Location

Centre Antoine LACASSAGNE

Nice, France

Location

Institut Curie

Paris, France

Location

Chu Poitiers

Poitiers, France

Location

Chu Rennes

Rennes, France

Location

CH Yves Le Foll

Saint-Brieuc, France

Location

René Huguenin

Saint-Cloud, France

Location

Chu Toulouse

Toulouse, France

Location

Chu Tours

Tours, France

Location

Related Publications (1)

• Miannay B, Minvielle S, Roux O, Drouin P, Avet-Loiseau H, Guerin-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. Sci Rep. 2017 Aug 23;7(1):9257. doi: 10.1038/s41598-017-09378-9.

  PMID: 28835615 RESULT

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Study Officials

• Philippe MOREAU, Pr

  Departement of clinical Hematology (University Hospital of Nantes)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2009
• First Posted: May 22, 2009
• Study Start: July 29, 2009
• Primary Completion: December 14, 2010
• Study Completion: July 14, 2016
• Last Updated: April 1, 2021

Record last verified: 2021-03

Locations

FR (26)