A Study of PAD Followed by Autologous Stem Cell Transplantation (ASCT) to Treat Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: PAD Followed by ASCT
Intervention description: Drug: Bortezomib, Bortezomib (1.3mg/m2, iv, on day 1, 4, 8, 11, of each 28 day cycle)
Drug: Adriamycin (Doxorubicin) /EPI, Adriamycin (Doxorubicin) (9 mg/m2, iv, on days 1-4 of each 28 day cycle) or EPI (15mg/m2, iv, on days 1-4 of each 28 day cycle)
Drug: Dexamethasone, Dexamethasone (20mg, iv, on days 1-4, 8-11of each 28 day cycle)
After received induction therapy, patients will proceed to receive ASCT based on the willing of the patients and the decision of the investigators.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Multiple myeloma; PAD; ASCT; Bone metabolites; Bone marker

Summary:

      This is a multicentre; single arm study in subjects with newly diagnosed multiple myeloma.

      The primary objectives of this study is to assess the effect of bortezomib combination
      therapy (PAD regimen) followed by ASCT on bone metabolites in patients with newly diagnosed
      multiple myeloma, as measured by ELISA methodology as previously described analyzing the
      change in biochemical bone marker compared with the baseline value: bone formation marker-
      bone alkaline phosphatase(bALP) and osteoblast inhibitor- Dickkopf-1(DKK-1）.

      The secondary objectives of this study are:

        1. Subgroup analysis for the change from baseline in biochemical bone marker based on
           whether or not Bisphosphonate was used.

        2. Assessment of other bone markers parameters: bone formation marker -carboxy terminal
           propeptide of type I procollagen (PICP); bone resorption markers -carboxy terminal
           telopeptide region of type I collagen ( ICTP); osteoclast stimulators
           -osteoprotegerin(OPG), soluble receptor activator of nuclear factor kappaB
           ligand(sRANKL);

        3. To observe the effect of bortezomib on bone mineral density (BMD) as measured by
           repeated quantitative CT-scan;

        4. The evaluation of Skeletal related events (SRE) and appearance of new bone lesions;

        5. To determine progression free survival (PFS), 1 year survival, overall survival and
           safety profile following treatment with PAD and ASCT as first-line therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Man or woman aged 18 to 65 years old;

          2. Subjects are newly diagnosed MM patients which are scheduled by the investigators to
             be treated with vincristine, adriamycin and dexamethasone standard therapy. Stage
             II/III (according to Durie and Salmon criteria) with skeletal involvement, such as
             bone pain, bone lytic lesions, diffuse osteoporosis or pathologic fractures;

          3. Life expectancy > 3 months;

          4. Patient has measurable disease in which to capture response, defined as one or more of
             the following;

               -  Serum M-protein level >10.0 g/L measured by serum protein electrophoresis or
                  immunoglobulin electrophoresis; or

               -  Urinary M-protein excretion > 1 g/24 hours; or

               -  Bone marrow plasmacytosis of > 30% by bone marrow aspirate and/or biopsy; or

               -  Serum free light chains (by the Freelite test) > 2 X the upper limit of normal
                  (ULN), in the absence of renal failure.

          5. Performance status (PS) of ECOG ≤2.0, unless PS of 3-4 based solely on bone pain;

          6. Patients must have a Platelets count≥50×109 cells /L; Absolute neutrophil count
             (ANC)≥0.75×109 cells /L;

          7. Patients must have adequate hepatic function defined as Alanine transaminase(ALT) ≤
             2.5 × upper limit of normal(ULN); Aspartate transaminase (AST) ≤2.5×ULN; Total
             bilirubin ≤2×ULN;

          8. Patients must have adequate renal function defined as creatinine clearance >30 ml
             /min;

          9. Subjects (or their legally acceptable representatives) must have signed a informed
             consent document indicating that they understand the purpose of and procedures
             required for the study and are willing to participate in the study.

        Exclusion Criteria:

          1. Non-secretory MM, unless the patient has measurable lesions on computed tomography
             (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (PET);

          2. Peripheral neuropathy or neuropathy pain grade 2 or high as defined by National Cancer
             Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) Version 3;

          3. Uncontrolled or severe cardiovascular disease, including myocardial infarction (MI )
             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;

          4. History of allergy reaction attributable to compounds containing boron or mannitol;

          5. Any serious, active disease or psychiatric illness that could potentially interfere
             with the completion of treatment according to this protocol or the investigator's
             decision;

          6. Concurrent treatment with another investigational agent;

          7. Female subject who is pregnant or breast-feeding.