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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Intergroupe Francophone du Myelome.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Intergroupe Francophone du Myelome
ClinicalTrials.gov Identifier:
NCT00907452
First received: May 20, 2009
Last updated: June 18, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention
Myeloma
Drug: melphalan-prednisone-thalidomide
Drug: lenalidomide-dexamethasone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Intergroupe Francophone du Myelome:

Estimated Enrollment: 1555
Study Start Date: April 2009
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: melphalan-prednisone-thalidomide Drug: melphalan-prednisone-thalidomide
Active Comparator: lenalidomide-dexamethasone Drug: lenalidomide-dexamethasone

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00907452

Locations
France
CH ALBI
Albi, France
CHRU Angers
Angers, France
CH Côte basque
Bayonne, France
CH Blois
Blois, France
BORDEAUX
Bordeaux, France
Chalons sur Saone
Chalons sur Saone, 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, France
Sponsors and Collaborators
Intergroupe Francophone du Myelome
Investigators
Study Chair: Philippe MOREAU, Pr Departement of clinical Hematology (University Hospital of Nantes)
  More Information

No publications provided

Responsible Party: Principal investigator: AVET-LOISEAU Hervé, University Hospital, Nantes
ClinicalTrials.gov Identifier: NCT00907452     History of Changes
Other Study ID Numbers: IFM 2007-03, Eudract: 2008-003486-58
Study First Received: May 20, 2009
Last Updated: June 18, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Intergroupe Francophone du Myelome:
Pharmacogenomics
prediction response
prediction adverse event

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
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
Lenalidomide
Melphalan
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 22, 2014