VELCADE-Thalidomide-Dexamethasone (VTD) vs Thalidomide-Dexamethasone (TD) Incorporated Into Double Autotransplantation for Untreated Multiple Myeloma (MM)

Thalidomide-Dexamethasone (TD) is a standard induction therapy for Multiple Myeloma (MM). The present study is designed to compare TD with VELCADE-Thalidomide-Dexamethasone (VTD) as induction therapy in preparation for, and as consolidation after, melphalan-based double autologous stem cell transplantation for previously untreated patients aged ≤65 years with symptomatic MM. Primary study endpoint is the rate of complete response (CR) plus near-complete response (nCR) to induction treatment. Secondary endpoints include the rate of CR plus nCR to double transplantation and subsequent consolidation therapy, time to progression (TTP), progression-free survival (PFS),overall survival (OS) and toxicity profile of both VTD and TD.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion criteria:

* Confirmed diagnosis of symptomatic MM based on standard criteria.
* No prior or current systemic therapy for MM, including steroids.
* At least 18 years and less than 65 years of age.
* Presence of quantifiable M protein in serum (e.g. greater than 1 g/dL for IgG MM, greater than 0.5 g/dL of IgA or IgD MM) or urine (e.g. greater than 200 mg/day for BJ MM).
* Karnofsky performance status (PS) at least 60%.
* Willing and able to comply with the protocol requirements.
* Agreement from both male and female patients to follow the risk management program established for the prevention of pregnancy, including double methods for contraception and beta-HCG tests for women of childbearing potential and contraception for males.
* Adequate organ function, including heart, liver, kidney (serum creatinine less than 2 mg/dL)
* Platelet count at least 70 x 10/mcL and absolute neutrophil count at least 1 x 10/mcl

Exclusion criteria:

* Diagnosis of asymptomatic MM or of MGUS based on standard criteria.
* Diagnosis of non-secretory MM.
* Diagnosis of AL Amyloidosis.
* Prior or current systemic therapy for MM, including steroids (with exception of bisphosphonates).
* Patient has received other investigational drugs within 30 days before enrollment.
* Female subjects pregnant or breastfeeding
* Patient has Grade 2 or higher peripheral neuropathy (NCI criteria).
* Patient has a prior history of thrombosis or venous thromboembolism or pulmonary embolism.
* Patient has a previous diagnosis of antiphospholipid antibodies or lupus anticoagulant, factor V Leiden mutation, prothrombin G21210A mutation, antithrombin, protein C or S deficiency.
* Patient has a clear indication to receive a specific other anti-platelet therapy (e.g. clopidogrel, ticlopidine).
* Patient has a clear indication to receive long-term anticoagulant therapy (e.g. prosthetic heart valve, atrial fibrillation).
* Active bleeding or high risk of bleeding (gastrointestinal bleeding within the past 12 months; endoscopic diagnosis of peptic ulcer disease or ulcerative esophagitis within the past 6 months unless there is documented endoscopic evidence of healing; intracranial bleeding within the past year; amyloidosis; known bleeding diathesis).
* Seropositive for HIV, or active hepatitis A, B or C infection.
* Poorly controlled hypertension or diabetes mellitus (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before the start of therapy) or other serious medical or psychiatric conditions that could interfere with adherence to or completion of this study.
* Patient has hypersensitivity to bortezomib, boron or mannitol.
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study
* Previous or concurrent malignancies at other sites, with the exception of appropriately treated localized epithelial skin or cervical cancer. Patients with remote histories (\>5 years) of other cured tumors may be entered.
* Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrolment.

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