Velcade, Melphalan, Prednisone And Thalidomide Versus Velcade, Melphalan, Prednisone in Multiple Myeloma Patients
Velcade, Melphalan, Prednisone And Thalidomide Versus Velcade, Melphalan, Prednisone in Multiple Myeloma Patients
The proposed study will evaluate whether the combination of VELCADE, Thalidomide , Melphalan
 and Prednisone (V-MPT), as induction treatment for newly diagnosed elderly MM patients,
 improves outcomes compared to the combination VELCADE-MP.
This phase III study represents a prospective randomized open label multicenter trial to
 evaluate whether the combination of VELCADE, Melphalan, Prednisone and Thalidomide (V-MPT),
 as induction treatment for newly diagnosed elderly MM patients, improves outcomes compared to
 the combination VELCADE-MP.

 Subjects will be randomized in a 1:1 allocation between:

 Arm A: 250 patients: V-MPT treatment Arm B: 250 patients: V-MP treatment Patients excluded
 from randomization are to be registered in Arm C. Patients randomized in arm A (Thalidomide
 based) will be further enrolled in the sub-study about the DVT prophylaxis.

 Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment,
 treatment and long-term follow-up (LTFU).

 1. Pre-treatment period:

 Screening visits, performed at study entry. After providing written informed consent to
 participate in the study, patients will be evaluated for study eligibility After
 registration subjects will be randomized.

 2. Treatment period:

 Subjects in Arm A will receive:

 1. Induction therapy:

 nine 5-week courses of VELCADE/Melphalan/Prednisone/Thalidomide (V-MPT)

 2. Maintenance therapy:

 Thalidomide in combination with VELCADE

 Subjects in Arm B will receive:

 1. Induction therapy:

 nine 5-week courses of VELCADE/Melphalan/Prednisone (V-MP)

 2. No maintenance therapy is scheduled At the end of induction treatment or at the
 time of discontinuation of all study drugs, all patients are to attend study center
 visits on an every 6 to 8-week basis, until development of confirmed Progressive
 Disease (PD)

 3. LTFU period:

 After development of confirmed PD all patients are to be followed for survival every 3 months
 via telephone or office visit.
Inclusion Criteria:

 -  Age > 65 year old and not a candidate for stem cell transplant, or younger who refuses
 or is not eligible for high-dose therapy

 -  Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or
 tissue damage

 -  Presence of measurable disease

 -  Karnofsky performance status (PS) > 60%

 -  Able to read and complete the HRQOL instruments

 -  Agrees to use an acceptable barrier method for contraception for the duration of the
 study

 -  Pretreatment clinical laboratory values within 14 days of randomization:

 platelet count ≥ 100x109/L

 -  hemoglobin ≥ 8 g/dL

 -  absolute neutrophil count (ANC) ≥ 1.0x109/L

 -  AST ≤ 2.5 times the upper limit of normal

 -  ALT ≤ 2.5 times the upper limit of normal

 -  total bilirubin ≤ 1.5 times the upper limit of normal

 -  serum creatinine ≤ 2.5mg/dL

 -  corrected serum calcium <14 mg/dL (<3.5 mmol/L)

 -  Subjects (or their legally acceptable representatives) must have signed an informed
 consent document indicating that they understand the purpose of and procedures
 required for the study and are willing to participate in the study.

 -  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;

 -  Males must agree to use barrier contraception (latex condoms) when engaging in
 reproductive activity during the Treatment Period and for 4 weeks after the last dose.

 Exclusion Criteria:

 -  Diagnosis of smoldering multiple myeloma or MGUS.

 -  Diagnosis of Waldenstrom's disease

 -  Prior or current systemic therapy for multiple myeloma including steroids (with
 exception of emergency use of a short course [maximum 4 days] of steroids before
 randomization or prior or current use of biphosphonates)

 -  Radiation therapy within 30 days before randomization

 -  Plasmapheresis within 30 days before randomization

 -  Major surgery within 30 days before randomization (Kyphoplasty is not considered major
 surgery)

 -  History of allergic reaction attributable to compounds containing boron or mannitol,
 or to Thalidomide

 -  Peripheral neuropathy Grade 2 or higher, as defined by National Cancer Institute
 Common Toxicity Criteria (NCI CTC) 3.0

 -  Uncontrolled or severe cardiovascular disease including myocardial infarction within 6
 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure,
 uncontrolled angina, clinically significant pericardial disease, or cardiac
 amyloidosis

 -  Other malignancy within the past 5 years. Exceptions: basal cell or non metastatic
 squamous cell carcinoma of the skin, cervical carcinoma in situ or FIGO Stage 1
 carcinoma of the cervix

 -  Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled
 diabetes, pulmonary disease) that is likely to interfere with study procedures or
 results, or that in the opinion of the investigator would constitute a hazard for
 participating in this study

 -  Use of any investigational drugs within 30 days before randomization.

 -  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).