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

Sponsor

Intergroupe Francophone du Myelome (Other)

Overall Status

Completed

CT.gov ID

NCT00907452

Collaborator

(none)

143

Enrollment

Locations

Arms

83.5

Actual Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myeloma	Drug: melphalan-prednisone-thalidomide Drug: lenalidomide-dexamethasone	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

143 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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

Actual Study Start Date :

Jul 29, 2009

Actual Primary Completion Date :

Dec 14, 2010

Actual Study Completion Date :

Jul 14, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: melphalan-prednisone-thalidomide	Drug: melphalan-prednisone-thalidomide
Active Comparator: lenalidomide-dexamethasone	Drug: lenalidomide-dexamethasone

Arm

Intervention/Treatment

Active Comparator: melphalan-prednisone-thalidomide

Drug: melphalan-prednisone-thalidomide

Active Comparator: lenalidomide-dexamethasone

Drug: lenalidomide-dexamethasone

Outcome Measures

Primary Outcome Measures

best response to treatment [1 year]
best response rate

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country
1	CH ALBI	Albi	France
2	CHRU Angers	Angers	France
3	CH Côte basque	Bayonne	France
4	CH Blois	Blois	France
5	BORDEAUX	Bordeaux	France
6	Chalon sur Saone	Chalon-sur-Saône	France
7	CHU Dijon	Dijon	France
8	Ch Dunkerque	Dunkerque	France
9	Chu Grenoble	Grenoble	France
10	CHD Vendée	La Roche Sur Yon	France
11	CHRU Lille	Lille	France
12	CHU LYON	Lyon	France
13	LYON SUD	Lyon	France
14	Ipc Marseille	Marseille	France
15	CHR METZ	Metz	France
16	CH Mulhouse	Mulhouse	France
17	Chu Nancy	Nancy	France
18	Chu Nantes	Nantes	France
19	Centre Antoine LACASSAGNE	Nice	France
20	Institut Curie	Paris	France
21	Chu Poitiers	Poitiers	France
22	Chu Rennes	Rennes	France
23	CH Yves Le Foll	St Brieuc	France
24	René Huguenin	St CLOUD	France
25	Chu Toulouse	Toulouse	France
26	Chu Tours	Tours	France