Cyclophosphamide, Lenalidomide and Dexamethasone (CRD) Versus Melphalan (200 mg/m2) Followed By Autologous Stem Cell Transplant (ASCT) In Newly Diagnosed Multiple Myeloma Subjects

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

This is a multicenter, randomized, open label study designed to compare the efficacy and safety of lenalidomide with low-dose alkylating agents versus high-dose melphalan followed by stem cell support in newly diagnosed symptomatic MM patients who are 65 years of age or younger.

Inclusion Criteria:

Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.

• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

• 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 test.
  • 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.

Exclusion Criteria:

• 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.