Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Bortezomib; Dexamethasone; Melphalan; Prednisone; Thalidomide
Intervention description: Bortezomib bolus intravenous (IV) injection; Dexamethasone for oral administration; Melphalan for oral administration; Prednisone for oral administration; Thalidomide for oral administration
Intervention MeSH terms: Thalidomide; Dexamethasone; Prednisone; Bortezomib; Melphalan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 502.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a randomized, open label, multicenter clinical trial to compare the efficacy and
      safety of Velcade (bortezomib) and dexamethasone versus Velcade, thalidomide, and
      dexamethasone versus Velcade, melphalan, and prednisone in patients with previously untreated
      multiple myeloma not considered candidates for high-dose chemotherapy and autologous stem
      cell transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female 18 years of age or older

          -  Not a candidate for high-dose chemotherapy and stem cell transplantation (HDT/SCT) due
             to age, presence of important comorbid condition(s) likely to have a negative impact
             on tolerability of HDT-SCT, or subject preference.

          -  A Karnofsky Performance Status score of ≥50%

          -  Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or
             tissue damage.

          -  Asymptomatic multiple myeloma-related organ or tissue damage can include presence of
             an asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia (hemoglobin
             <10 g/dL), renal function impairment (serum creatinine > upper limit of normal [ULN])
             or hypercalcemia (serum calcium >ULN).

          -  Must have measurable disease requiring systemic therapy. Measurable disease is defined
             by at least 1 of the following criteria:

               -  Quantifiable serum M-protein value (>1 g/dL of immunoglobulin (Ig)G or IgM
                  M-protein, >0.5g/dL of IgA M-protein, >0.5 g/dL of IgD M-protein)

               -  Urine light-chain excretion ≥200 mg/24 hours

          -  Voluntary written informed consent must be given before performance of any study
             related procedure not part of normal medical care, with the understanding that consent
             may be withdrawn by the participant at any time without prejudice to future medical
             care.

        Exclusion Criteria:

          -  Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined
             significance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiple
             myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum
             monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and
             renal insufficiency related to the monoclonal protein; and (if determined) proportion
             of plasma cells in the bone marrow of 10% or less.

          -  Diagnosis of Waldenström's disease or other conditions in which immunoglobulin M (IgM)
             M-protein is present in the absence of a clonal plasma cell infiltration or lytic bone
             lesions.

          -  Previously or currently treated with any systemic therapy for multiple myeloma. Prior
             treatment of hypercalcemia or spinal cord compression with corticosteroids or
             radiation therapy, respectively, does not disqualify the subject (the dose of
             corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week
             period).

          -  Radiation therapy within 2 weeks before randomization. Enrollment of patients who
             require concurrent radiotherapy (which must be localized in its field size) should be
             deferred until the radiotherapy is completed and 2 weeks have elapsed since the last
             date of therapy.

          -  Major surgery within 30 days before randomization (Kyphoplasty is not considered major
             surgery)

          -  History of allergy to any of the study medications, their analogues, or excipients in
             the various formulations

          -  ≥Grade 2 peripheral neuropathy on clinical examination within 21 days before
             enrollment.

          -  Any of the following clinical laboratory values within 21 days prior to enrollment:

               -  Absolute neutrophil count (ANC) <1000 cells/mm^3

               -  Platelets <100,000 × 10^9/L, or <70 × 10^9/L if thrombocytopenia is considered by
                  the investigator to be due to myeloma infiltration of bone marrow

               -  Aspartate aminotransferase [serum glutamic oxaloacetic transaminase] (AST [SGOT])
                  or alanine aminotransferase [serum glutamic-pyruvic transaminase] (ALT [SGPT])
                  >2× the upper limit of normal (ULN)

               -  Serum creatinine >2 mg/dL (>176.8 µmol/L); if the rise in creatinine is related
                  to myeloma and there has been demonstrated a response to hydration, the subject
                  may be enrolled.

          -  Myocardial infarction within 6 months prior to enrollment or New York Hospital
             Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or
             significant conduction system abnormalities in the opinion of the investigator. Prior
             to study entry, any abnormality on electrocardiogram at screening must be determined
             and documented by the investigator as not medically relevant.

          -  Any condition, including laboratory abnormalities, that in the opinion of the
             Investigator places the patient at unacceptable risk if he/she were to participate in
             the study. This includes but is not limited to serious medical conditions or
             psychiatric illness likely to interfere with participation in this clinical study.

          -  Prior malignancy except for adequately treated basal cell or squamous cell skin
             cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, or
             other cancer for which the patient has been disease-free for at least 3 years.

          -  Female who is pregnant or breastfeeding. Female participants of childbearing potential
             must have a negative pregnancy test with a sensitivity of at least 50 mIU/mL during
             Screening.

          -  Use of any investigational drugs within 30 days before randomization.