A Phase 3, Multicentre, Randomized, Controlled Study to Determine the Efficacy and Safety of Cyclophosphamide, Lenalidomide and Dexamethasone (CRD) 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 protocol
- 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consent may be withdrawn by the patient at any time without prejudice to their future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
- Women of child-bearing potential must agree to use 2 methods of contraception: 1
effective (for example hormonal or tubal ligation) and 1 barrier (for example latex
condom, diaphragm) for at least 4 weeks before starting the therapy, during the
Treatment Period, and for 4 weeks after the last dose of lenalidomide
- 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.
- Negative serum beta-human chorionic gonadotropin ( beta-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
- Patient was diagnosed with symptomatic multiple myeloma based on standard criteria
(10), 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 HBV, HCV and HIV negative test.
- Patients must have normal ECG and NYHA ≤ 2; an evaluation of ejection fraction by
ECHO or MUGA is optional
- Patients must normal chest X ray; an evaluation of pulmonary function studies on
mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) is optional.
- 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: ≥ 20 mL/minute
- Patient has a baseline bone marrow sample available for cytogenetics, that will
be processed and eventually centralized.
- 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 women. A serum β-hCG pregnancy test must be performed at the
Screening visit, for female patients of child-bearing potential. If the test is
positive, the patient must be excluded from the study. Confirmation that the patient
is not pregnant must be established by a negative serum or urinary pregnancy test
with the result obtained 1 day prior to the Baseline visit (or the day of the visit
if results are available before drug delivery). A pregnancy test is not required for
naturally post-menopausal women (who have not had menses at any time in the preceding
24 consecutive months) or surgically sterilised women (hysterectomy, bilateral
ovariectomy, bilateral salpingectomy);
- 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)
- Patients previously diagnosed as bearing deep venous thrombosis or arterial
thromboembolic event within the latest 12 months.