Please select the eligibility criteria that correspond to the clinical trial below.
Title: A National, Open-Label, Multicenter, Randomized, Comparative Phase III Study of Induction Treatment With VBMCP-VBAD/Velcade Versus Thalidomide / Dexamethasone Versus Velcade / Thalidomide / Dexamethasone Followed by High Dose Intensive Therapy With Autologous Hemopoietic Stem Cell Support and Maintenance Treatment With Interferon-a Versus Thalidomide Versus Thalidomide / Velcade in Untreated Patients With Multiple Myeloma Less Than 65 Yrs Old
Brief Summary: The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone. The second one is to evaluate the ability of stem cell mobilization after the treatments in order to do an autologous transplant. Otherwise this study wants to compare the safety and efficacy of the maintenance treatments: Interferón a-2b versus Thalidomide versus Thalidomide/Velcade.


Options:
A: Inclusion Criteria:

1. Male or female subjects 18 years or older
2. Diagnosis of multiple myeloma
3. Measurable, secretory multiple myeloma defined as serum monoclonal IgG of ≥10 g/L, serum monoclonal IgA or IgE ≥5 g/L, or serum monoclonal IgD ≥0.5g/L; or urine M-protein of ≥200 mg/24 hr
4. Relapse or progression of myeloma following prior systemic antineoplastic therapy.

Exclusion Criteria:

1. Previous treatment with VELCADE
2. More than 3 previous lines of therapy (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a greater than 6 month treatment-free interval)
3. Peripheral neuropathy or neuropathic pain of NCI CTCAE Grade ≥2
4. Any of the following within 3 weeks prior to randomization:

   antineoplastic or experimental therapy, corticosteroid use above 10mg a day (prednisone or equivalent), or plasmapheresis
5. Any of the following within 2 weeks prior to randomization:

   radiation therapy, major surgery (kyphoplasty is not considered major surgery)
6. Prior malignancy other than multiple myeloma diagnosed or treated within the last 2 years, with the exception of completely resected carcinoma in situ or basal/squamous carcinoma of the skin
B: Inclusion Criteria:

* Voluntary written informed consent
* Male or female subject 18 years of age or older
* A Karnofsky Performance Status score of ≥50% (Eastern Cooperative Oncology Group Performance Status score ≤2)
* Subjects must have symptomatic myeloma or asymptomatic myeloma with myeloma-related organ damage
* Diagnosed Multiple myeloma
* Subjects must have measurable disease requiring systemic therapy
* Subjects must not have been treated previously with any systemic therapy for multiple myeloma
* Two weeks must have elapsed since the date of the last radiotherapy treatment
* Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (1 highly effective method and 1 additional effective method) used at the same time, beginning at least 4 weeks before initiation of Revlimid treatment. Women must also agree to ongoing pregnancy testing
* Men must agree to not father a child and agree to use a latex condom during therapy and for 4 weeks after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential
* All subjects must agree to comply with the requirements of the RevAssistSM program

Exclusion Criteria:

* History of allergy to any of the study medications, their analogues, or excipients in the various formulations
* ≥Grade 2 peripheral neuropathy on clinical examination
* Myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities.
* Female subject who is pregnant or breast-feeding
* Clinically relevant active infection or serious comorbid medical conditions
* Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical or psychiatric illness likely to interfere with participation in this clinical study
* Active prior malignancy diagnosed or treated within the last 3 years
C: Inclusion Criteria:

1. Must be able to comply with the protocol requirements
2. Must voluntary sign the informed consent before performance of any study-related procedure not part of normal medical care,
3. Age \<65 years and possibly to do an autologous transplant.
4. Patient recently diagnosed with symptomatic Multiple Myeloma who has not received any previous chemotherapy treatment for Multiple Myeloma.
5. Patient has a measurable disease defined as quantifiable serum monoclonal protein value and, where applicable, urine Light-chain excretion of ≥ 200 mg/24 hours.
6. ECOG \< 2.
7. El patient has a life-expectancy \> 3 months.
8. Patient has the following laboratory values before beginning induction treatment:

   1. Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g/dl and absolute neutrophil count ≥ 1000/mm3. Lower values are allowed if they are due to marrow infiltration.
   2. Corrected serum calcium \<14mg/dl.
   3. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
   4. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal.
   5. Total bilirubin: ≤1.5 x the upper limit of normal.
   6. Serum creatinine ≤ 2 mg/dl.
9. For Patients included in Thalidomide branches: women of childbearing age must not have sex unless they use two anticonceptive methods beginning 4 weeks before the first dose, during all the study until 4 weeks after the last one.

Exclusion Criteria:

1. Non-secretor Myeloma.
2. Patients previously received treatment to Multiple Myeloma, except steroids doses for urgency or bisphosphonates or radiotherapy before beginning treatment.
3. Patients with \< Grade 2 peripheral neuropathy within 14 days before enrolment.
4. Patient had major surgery within 4 weeks before enrolment.
5. Patient has hypersensitivity to bortezomib, boron or mannitol or Thalidomide.
6. Patient has received other investigational drugs within 30 days before enrolment.
7. Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.
8. Patient had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
9. Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
10. Pregnancy or breast-feed women.
D: 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

Answer: C