Sequential VAD and VTD Followed by HDT With ASCT and Velcade Maintenance for NDMM
Sequential VAD and VTD Followed by HDT With ASCT and Velcade Maintenance for NDMM
1. Primary Objective To assess the response rate of sequential VAD (Vincristine,
 Adriamycin, Dexamethasone) and VTD (Velcade, Thalidomide, Dexamethasone) induction
 therapy as a first line treatment for the patients with multiple myeloma

 2. Secondary Objectives

 1. To assess the progression free survival, duration of response, and overall survival
 of patients given sequential VAD and VTD induction followed by high dose therapy
 with autologous stem cell transplantation and maintenance treatment with Velcade

 2. To assess the toxicities of sequential VAD and VTD induction chemotherapy, high
 dose therapy with autologous stem cell transplantation, and of maintenance
 treatment with Velcade.
1. Overview of study design

 This study aims to assess the efficacy and toxicities of sequential VAD and VTD
 induction followed by high dose therapy with autologous stem cell transplantation and
 maintenance treatment with velcade as a first line treatment for the patients with
 multiple myeloma. This study will be conducted as an open, multi-center, single arm,
 prospective phase 2 study.

 2. Sample size determination

 The expected response rate of sequential VAD and VTD induction chemotherapy as a first
 line treatment for the patients with multiple myeloma is 80%. By using Flemming's single
 stage design ( error: 0.05,  error : 0.2), 55 evaluable patients are needed to prove
 this hypothesis. If withdrawal rate is 10%, enrollment of total 62 patients will be
 needed.

 3. Duration of the Study

 One year of enrollment will be needed (2006.03.1-2007.02.28). At least 24 months of follow-up
 for the patients who are to be enrolled last time is needed.
Inclusion Criteria:

 -  1.Previously untreated newly diagnosed patients with MM (stage II-III) 2.Age < 65
 3.Eastern Cooperative Oncology Group Performance Status 0-1 4.EF > 50%, FVC and FEV >
 50%, DLCO >50% 5.Platelet count ≥ 100 x 109/L (pretreatment platelet transfusion is
 not allowed, while transfusion during the treatment is permitted), hemoglobin ≥ 8 g/dL
 (≥ 4.96 mol/L), Prior RBC transfusion or recombinant human erythropoietin use is
 allowed), absolute neutrophil count (ANC) ≥ 1.0 x 109/L 6.Adequate liver function
 (bilirubin < UNL(Upper Normal Limit) x 2 and ALT/AST < UNL x 3) 7.Adequate renal
 function (serum creatinine < UNL x 1.5 or creatine clearance > 60 ml/min) 8.Signed the
 informed consent, have the will and ability to follow the protocol

 Exclusion Criteria:

 -  1. History of allergic reaction attributable to compounds containing boron or mannitol
 2. Known hypersensitivity to thalidomide or dexamethasone 3. Peripheral neuropathy or
 neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3 4. Uncontrolled
 or severe cardiovascular disease, including 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 5. Acute severe
 infection requiring antibiotic therapy 6. Previous cancer history (except in situ
 carcinoma of cervix or basal cell cancer of skin) 7. Pregnancy or breastfeeding 8.
 Active ulcer detected by gastroscopy (gastroscopy is not routine in all patients, only
 to patients with symptoms of ulcer disease and/or history of previous ulcer therapy
 and/or physician's discretion) 9. Previous renal transplantation 10. Recurrent deep
 vein thrombosis or pulmonary embolism 11. Uncontrolled diabetes mellitus 12. Receipt
 of extensive radiation therapy within 4 weeks ((Extensive means RT to more than 2
 anatomic sites).