Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III, Prospective, Open Label, Multicenter, Randomized Trial of Melphalan, Prednisone and Thalidomide Versus Melphalan and Prednisone as First Line Therapy in Myeloma Patients Aged >65.
Brief Summary: The purpose of this study is to determine whether the association of Thalidomide to Melphalan and Prednisone is effective in the treatment of newly diagnosed elderly multiple myeloma.


Options:
A: Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

* Male or female
* Not a candidate for HDT/SCT due to: age - subject is 65 years or older or in subjects less than 65 years of age - presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT/SCT.
* Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage. Asymptomatic multiple myeloma-related organ or tissue damage can include presence of asymptomatic lytic bone lesion or plasmacytoma, or presence of anemia, renal function impairment, or hypercalcemia, as long as the criteria for pre-treatment clinical laboratory values indicated below are met.
* Presence of measurable disease, defined as:

  * For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value.
  * For oligosecretory or nonsecretory multiple myeloma, measurable disease is defined by the presence of measurable soft tissue or organ (not bone) plasmacytomas as determined by clinical examination or applicable radiographs.
* Karnofsky performance status score of equal or greater then 60%.
* Willing and able to complete the PRO instruments
* Agrees to use an acceptable barrier method for contraception for the duration of the study (for male subjects); If female subjects are still having menstrual periods and are not surgically sterile, they must be practicing an effective method of birth control before entry, and throughout the study, and have a negative serum B-HCG pregnancy test at screening.
* Have pretreatment clinical laboratory values meeting the criteria as described in the protocol within 14 days before randomization.
* Subjects (or their legally acceptable representatives) must have signed an 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:

Potential subjects who meet any of the following criteria will be excluded from participating in the study:

* Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less.
* Diagnosis of Waldenström's disease or other conditions in which IgM M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
* Prior or current systemic therapy for multiple myeloma including steroids (with the exception of emergency use of a short course \[maximum of 4 days\] of steroids before randomization or of prior or current use of bisphosphonates)
* Radiation therapy within 30 days before randomization
* Plasmapheresis within 30 days before randomization
* Major surgery within 30 days before randomization (kyphoplasty is not considered major surgery)
* History of allergic reaction attributable to compounds containing boron or mannitol
* Peripheral neuropathy or neuropathic pain Grade 2 or higher.
* Uncontrolled or severe cardiovascular disease, including myocardial infarction, within 6 months of enrollment, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
* Other malignancy within the past 5 years. Exceptions if treated and not active include the following: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix
* Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes) that is likely to interfere with study procedures or results, or that, in the opinion of the investigator would constitute a hazard for participating in this study
* Use of any investigational drugs within 30 days before randomization
* Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or family members of the employees or the investigator.
B: Inclusion Criteria:

* untreated myeloma patients
* age \>65 years of age or younger but excluded from transplant procedure
* Durie \& Salmon stage II or III myeloma and measurable disease.
* Patients agreed to use contraception

Exclusion Criteria:

* other cancer
* psychiatric disease and any grade 2 peripheral neuropathy
C: DISEASE CHARACTERISTICS:

* Previously untreated multiple myeloma

  * Stage I, II, or III disease by the International Staging System
* Measurable M-protein as defined by 1 of the following:

  * Serum M-protein at least 1.0 g/dL by serum protein electrophoresis or immunoelectrophoresis
  * Urinary M-protein excretion at least 200 mg/24 hours
* No nonsecretory multiple myeloma
* Not planning to undergo future autologous stem cell transplantation

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-3\* NOTE: \*Zubrod 3 allowed only if multiple myeloma is the central cause of disability

Life expectancy

* Not specified

Hematopoietic

* Platelet count at least 80,000/mm\^3\*
* Absolute neutrophil count at least 1,000/mm\^3\*
* Hemoglobin at least 9 g/dL\* (epoetin alfa or transfusion allowed) NOTE: \*Unless due to greater than 50% marrow involvement by myeloma on biopsy

Hepatic

* AST/ALT no greater than 3 times upper limit of normal\* NOTE: \*Values outside of this range are allowed at the investigator's discretion

Renal

* Creatinine no greater than 2.5 mg/dL\* NOTE: \*Values outside of this range are allowed at the investigator's discretion

Cardiovascular

* No New York Heart Association class III or IV heart failure
* No myocardial infarction within the past 6 months
* No poorly controlled hypertension

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment

  * Female patients must use 2 reliable forms of contraception simultaneously
  * Male patients must use effective barrier contraception
* No uncontrolled active infection requiring IV antibiotics
* No poorly controlled diabetes mellitus that would preclude ability to take oral glucocorticoids
* No other serious medical condition that would preclude study participation
* No psychiatric illness that would preclude study participation
* No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* Must be able to take aspirin by mouth at a dose of 325 mg per day or enoxaparin subcutaneously at a dose of 40 mg per day as a form of thrombotic prophylaxis, except if already on therapeutic anticoagulant medication

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior interferon or thalidomide

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Prior high-dose dexamethasone allowed provided duration of administration was no more than 4 days

Radiotherapy

* Prior localized radiotherapy allowed provided it was not to the sole site of evaluable disease

Surgery

* Not specified

Other

* No prior treatment for clinically significant ventricular cardiac arrhythmias
* Concurrent bisphosphonates allowed
D: Inclusion Criteria:

* Must be able to comply with the protocol requirements.
* Must voluntary sign the informed consent before performance of any study-related procedure not part of normal medical care, with the understanding it can be withdrawn at any time without prejudice to future medical care.
* Age \> 65 years.
* Patient recently diagnosed with symptomatic Multiple Myeloma based on standard criteria28 and that has not received any previous chemotherapy treatment for Multiple Myeloma Some steroid doses or bisphosphonates are allowed for emergencies before starting induction treatment.
* Patient has measurable disease, defined as follows:

For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24 hours.

* Patient has a ECOG performance status \< 2
* Patient has a life-expectancy \>3 months.
* Patient has the following laboratory values before beginning induction treatment:

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.

Corrected serum calcium \<14mg/dl. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal. Total bilirubin: ≤1.5 x the upper limit of normal. Serum creatinine ≤ 2 mg/dl.

Exclusion Criteria:

* Patients previously received treatment to Multiple Myeloma, except steroids doses for urgency or bisphosphonates.
* Non-secretor Myeloma
* Patients with \< Grade 2 peripheral neuropathy within 14 days before enrolment.
* Patient had major surgery within 4 weeks before enrolment.
* Patient has hypersensitivity to bortezomib, boron or mannitol.
* Patient has received other investigational drugs within 30 days before enrolment.
* Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.
* 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.
* Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.

Answer: B