A Study to Evaluate Two Different Regimens of VELCADE in Combination With Dexamethasone, Thalidomide and Cyclophosphamide (VDT vs VDTC) in Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: bortezomib, dexamethasone, and thalidomide; bortezomib, dexamethasone, thalidomide, and cyclophosphamide
Intervention description: VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy (HDT) and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21)
Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.
Thalidomide will be given by mouth (p.o.)every day, starting on Day 1 of Cycle 1 (e.g. the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).; VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy(HDT)and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21).
Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.
Thalidomide will be given by mouth (p.o.) every day, starting on Day 1 of Cycle 1 (e.g., the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).
Cyclophosphamide will be given as an intravenous (i.v.) dose of 400 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for a total of 4 cycles.
Intervention MeSH terms: Thalidomide; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Bortezomib; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 98.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this Phase 2 randomized study is to evaluate the efficacy and safety of
      treatment with a regimen of VELCADE, dexamethasone, and thalidomide (VDT) or VELCADE,
      dexamethasone, thalidomide, and cyclophosphamide (VDTC) in subjects with newly diagnosed
      symptomatic multiple myeloma who have received no prior treatment and are candidates to
      receive high-dose therapy and autologous bone marrow/stem cell transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between ≥18 and ≤70 years

          -  Patient is a candidate for HDT combined with an autologous SCT

          -  Karnofsky Performance Status score of ≥60%

          -  Multiple myeloma diagnosed according to the following standard criteria AND requiring
             systemic therapy:

          -  Presence of M-component in serum and/or urine, plus clonal plasma cells in the bone
             marrow and/or a documented clonal plasmacytoma

          -  PLUS 1 or more of the following:

               1. Calcium elevation (>11.5 mg/dL or >2.65 mmol/L)

               2. Renal insufficiency (creatinine >2 mg/dL or >177 umol/L)

               3. Anemia (hemoglobin <10 g/dL [<12.5 mmol/L] or at least 2 mg/dL [1.25 mmol/L]
                  below normal)

               4. Bone disease (lytic lesions or osteopenia)

          -  AND fulfill criteria for measurable disease, as defined by at least 1 of the following
             3 measurements:

               1. Serum M-protein ≥1 g/dL (≥10 g/L)

               2. Urine M-protein ≥200 mg/24 h

               3. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L)
                  provided serum FLC ratio is abnormal

          -  Women of childbearing potential must agree to use 2 methods of contraception.

          -  Males must agree to use barrier contraception.

          -  Subjects (or their legally acceptable representatives) must have signed an informed
             consent document.

          -  To participate in the optional pharmacogenomic component of this study, subjects (or
             their legally acceptable representative) must have signed the informed consent form.
             Refusal to consent for this component does not exclude a subject from participation in
             the clinical study.

        Exclusion Criteria:

          -  Diagnosis of smoldering OR non-secretory multiple myeloma or monoclonal gammopathy of
             undetermined significance (MGUS).

          -  Diagnosis of Waldenström's disease or other conditions in which IgM M-protein is
             present in the absence of a clonal plasma cell infiltration with lytic bone lesions.

          -  Prior or current systemic therapy for multiple myeloma including steroids.

          -  Radiation therapy and/or plasmapheresis within 15 days before randomization.

          -  History of allergic reaction attributable to compounds being given (VELCADE,
             thalidomide, dexamethasone, and/or cyclophosphamide) or compounds containing boron or
             mannitol.

          -  Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by National
             Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version
             3.0.

          -  Uncontrolled or severe cardiovascular disease

          -  Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled
             diabetes) 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 subjects of childbearing potential.

          -  Employees of the investigator or study center, with direct involvement in the proposed
             study or other studies under the direction of that investigator or study center, as
             well as family members of the employees or the investigator.