A PHASE 3, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF LENALIDOMIDE, MELPHALAN AND PREDNISONE (MPR) Versus MELPHALAN (200 mg/m2) FOLLOWED BY STEM CELL TRANSPLANT IN NEWLY DIAGNOSED MULTIPLE MYELOMA SUBJECTS
- Patient is, in the investigator(s) opinion, willing and able to comply with the
- Patient has given voluntary written informed consent before performance of any
study-related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to their future
- Patient is 65 years old or younger at the time of signing the informed consent
- Female patient is either post-menopausal or surgically sterilized or willing to use
an acceptable double method of birth control (i.e., a hormonal contraceptive,
intrauterine device, diaphragm with spermicide, condom with spermicide, or
abstinence) for the duration of the study.
- Negative serum β-human chorionic gonadotropin ( β-HCG) pregnancy test both 24 hours
prior to beginning of therapy and then at 4 weeks intervals in women with regular
menstrual cycles or every 2 weeks in women with irregular menstrual cycles during
study treatment for subjects of childbearing potential
- Male patient agrees to use an acceptable method for contraception (i.e., condom or
abstinence) during study drug therapy (including dose interruption) and for 4 weeks
after discontinuation of lenalidomide therapy.
- Patient was diagnosed with symptomatic multiple myeloma based on standard criteria
(9), and has measurable disease, defined as follows: any quantifiable serum
monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG
M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine
light-chain excretion of >200 mg/24 hours; measurable plasmacytoma > 2 cm as
determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan);
bone marrow plasma cells>10%.
- Patient has a Karnofsky performance status ≥ 60%.
- Patient has a life-expectancy > 6 months
- Patient has not active infectious hepatitis type B or C, and has HIV negative test
- Patients must have an ejection fraction by ECHO or MUGA > 50% performed within 60
days prior to registration
- Patients must have adequate pulmonary function studies > 50% of predicted on
mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted.
Patients unable to complete pulmonary function tests because of myeloma-related
chest pain, must have a high resolution CT scan of the chest and must also have
acceptable arterial blood gases defined as P02 greater than 70.
- Patient has the following laboratory values within 14 days before Baseline (day 1 of
the Cycle 1):
- Platelet count ≥ 75 x 109/L without transfusion support within 7 days before the
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without the use of growth factors.
- Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).
- Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN).
- Alanine transaminase (ALT): ≤ 2.5 x the ULN.
- Total bilirubin: ≤ 1.5 x the ULN.
- Calculated or measured creatinine clearance: ≥ 30 mL/minute
- Patient has a baseline bone marrow sample available for cytogenetics, that will be
processed and eventually centralized within each country.
- Previous treatment with anti-myeloma therapy (does not include radiotherapy,
bisphosphonates, or a single short course of steroid; < to the equivalent of
dexamethasone 40 mg/day for 4 days).
- Any serious medical condition, including the presence of laboratory abnormalities,
which places the subject at an unacceptable risk if he or she participates in this
study or confounds the experimental ability to interpret data from the study.
- Pregnant or lactating females.
- 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 histologic finding of prostate
cancer (TNM stage of T1a or T1b)
- Neuropathy of ≥ grade 2 severity.
- Patients previously diagnosed as bearing deep venous thrombosis or arterial
thromboembolic event within the latest 12 months, or bearing a clear indication for
anti-platelet or anticoagulant therapy or bearing a high risk of bleeding
complications are ineligible for the sub-study protocol.