Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Prospective, Randomized Clinical Study of VELCADE-Thalidomide-Dexamethasone (VTD) Versus Thalidomide-Dexamethasone (TD) for Previously Untreated Multiple Myeloma (MM) Patients Who Are Candidates to Receive Double Autologous Transplantation
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* patients less than 61 years of age
* Durie Salmon stage II or III
* written and informed consent

Exclusion Criteria:

* Prior treatment for myeloma
* ECOG performance score of 4
* Positive HIV test
* Chronic respiratory disease (DLco \< 60%)
* Systolic ejection fraction \< 50%
* Pregnant or nursing women
B: Inclusion Criteria:

* Less 70 years
* ECOG 0-2
* Symptomatic MM (pain, anemia, infection, haemorrhage, loss of weight, hypercalcemia, extramedulary plasmocytoma, creatinine \>2 mg/dl).
* No previous chemotherapy

Exclusion Criteria:

* \>70 years
* ECOG 3-4
* myeloma quiescent
* cardiopathy
* liver disfunction
* HIV+
* Hepatitis B-C +
* Previous chemotherapy
C: Inclusion Criteria:

* Recently diagnosed MM according to the criteria of the South West Oncology Group (SWOG)
* Not previously treated, apart from local radiotherapy, in the case of a threatening or incapacitating lesion, and/or a 4-day block of dexamethasone (40 mg/mL) in an emergency
* Stage II or III disease according to the Durie and Salmon classification or Stage I disease with symptomatic bone lesion
* \< 65 years of age
* Ability to give signed informed consent
* Secretion of a measurable monoclonal spike (\> 10 g/l in the serum or 0.2 g/24h in the urine)
* Negative pregnancy test at inclusion (if necessary)
* Absence of active infection. In the case of infection, appropriate antibiotic therapy must be administered and patients must have been apyretic for 48 hours before the start of treatment with VAD or Velcade®/dexamethasone

Exclusion Criteria:

* ECOG performance status \> 2
* History of cancer (other than basal cell carcinoma or carcinoma of the cervix in situ)
* Life expectancy \< 2 months
* Confirmed amyloidosis
* Positive HIV serology
* Serious psychiatric item in the history
* Renal failure requiring dialysis
* Uncontrolled diabetes, contra-indicating the use of corticosteroids
* Peripheral neuropathy National Cancer Institute (NCI) grade \> 2 (Annex 5)
* Clinical signs of heart failure or coronary heart disease
* Bilirubin \> 3 x normal
* Transaminases or gamma-glutamyl transpeptidase (GT) \> 4 x normal
* Platelets \< 50 x 10\^9/l during the 15 days prior to inclusion
* Neutrophils \< 0.75 x 10\^9/l during the 15 days prior to inclusion
* Use of an investigational medicinal product during the 30 days prior to inclusion
* Known hypersensitivity to bortezomib, boron or mannitol
D: 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.

Answer: D