Please select the eligibility criteria that correspond to the clinical trial below.
Title: A PHASE III, MULTI-CENTER, RANDOMIZED OPEN LABEL STUDY OF VELCADE, MELPHALAN, PREDNISONE AND THALIDOMIDE (V-MPT) Versus VELCADE, MELPHALAN, PREDNISONE (V-MP) IN ELDERLY UNTREATED MULTIPLE MYELOMA PATIENTS
Brief Summary: The proposed study will evaluate whether the combination of VELCADE, Thalidomide , Melphalan and Prednisone (V-MPT), as induction treatment for newly diagnosed elderly MM patients, improves outcomes compared to the combination VELCADE-MP.


Options:
A: Inclusion Criteria:

* Patients must have newly diagnosed multiple myeloma with measurable disease; patients with non-secretory multiple myeloma (MM) based upon standard M-component criteria (i.e., measurable serum/urine M-component) are not eligible for this study; exception: patients with non-secretory MM will be eligible only if the baseline serum Freelite is elevated (Note that serum Freelite must be drawn; serum light chains are not acceptable); all tests for establishing baseline disease status must be completed within 28 days prior to registration and documented on the baseline and follow-up tumor assessment form for multiple myeloma
* Patients must have received no prior chemotherapy for this disease; patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis); prior steroid treatment is allowed provided treatment was not more than 2 weeks in duration; patients must not have received any prior treatment with bortezomib or lenalidomide
* Patients must have a Zubrod performance status (PS) of 0 - 3; NOTE: patients with PS 3 are eligible only if it is documented by the treating physician that the patient's multiple myeloma is the central cause of his/her disability; patients who have a PS of 3 due to other concurrent medical conditions are not eligible for this trial
* Platelet count \>= 80 x 10\^3/mcL; must be obtained within 28 days prior to registration; exception: patients with biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with \> 50% of the cells being malignant plasma cells (documented marrow results required); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients
* Absolute neutrophil count (ANC) \>= 1 x 10\^3/mcL; must be obtained within 28 days prior to registration; exception: patients with biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with \> 50% of the cells being malignant plasma cells (documented marrow results required); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients
* Hemoglobin (including patients who have been either transfused or treated with erythropoietin \[EPO\]) \>= 9 g/dL; must be obtained within 28 days prior to registration; exception: patients with biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with \> 50% of the cells being malignant plasma cells (documented marrow results required); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients
* Patients must be offered participation in the Myeloma Specimen Repository for banking and future research; with the patient's consent, bone marrow aspirates and serum specimens will be submitted to the Myeloma Specimen Repository for additional testing and banking (including SNP testing); patient consent must be obtained before specimens may be submitted
* Patients must have baseline skeletal survey to include lateral skull, anterior-posterior (AP) pelvis and posterior-anterior (PA) chest within 28 days prior to registration
* Institutions must submit a local cytogenetics report and fluorescence in situ hybridization (FISH) analysis report obtained prior to enrollment to S0777; for FISH analysis two probes will be utilized: LSI 13 (RBI) 13q14 SpectrumOrange Probe for detection of chromosome 13 deletion and LSI p53 (17p13.1) SpectrumOrange probe for detection of tumor protein (p)53 locus on chromosome 17; if these exact probes are not available locally, it is acceptable to submit results using local protocol; this must be noted on the prestudy form; NOTE: it is not required that the results of the FISH analysis be known prior to registration, only that pre-registration specimens be drawn and sent for analysis prior to registration, and the FISH analysis report be submitted
* Patients with pathologic fractures, pneumonia at diagnosis or symptomatic hyperviscosity must have these conditions attended to prior to registration (i.e., intramedullary rod, I.V. antibiotics, plasmapheresis)
* Patients must have a calculated or measured creatinine clearance \> 30 cc/min; measured creatinine clearance or serum creatinine used in calculation must be obtained within 28 days prior to registration
* Patients must not have uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, myocardial infarction within the last 6 months, history of treatment for clinically significant ventricular cardiac arrhythmias, poorly controlled hypertension, or poorly controlled diabetes mellitus; patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration
* Patients must not have any psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
* Patients must not be hepatitis B, hepatitis C or human immunodeficiency virus (HIV) positive; patients must have a negative hepatitis B and HIV test performed within 28 days prior to registration; exception: treatment-sensitive HIV infection patients will be eligible provided that immunological and virologic indices are indicative of favorable long-term survival prospects on the basis of HIV infection, but whose life expectancy is limited predominantly by multiple myeloma rather than HIV infection in the judgment of the treating physician
* Patients must not have a history of cerebral vascular accident with persistent neurologic deficits
* Patients must be able to take aspirin 325 mg daily (or enoxaparin 40 mg subcutaneously \[SQ\] daily if patient is unable to take aspirin) as prophylactic anticoagulation; exception: patients receiving anticoagulation therapy such as Coumadin or heparin will NOT receive aspirin, and therefore need not be able to take it
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
* No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for five years
* Patients must be offered participation in gene expression profiling (GEP) molecular studies for the evaluation of genetic polymorphisms
* All patients must be informed of the investigational nature of this study and must sign and give written consent in accordance with institutional federal guidelines
* At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the statistical center in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
B: Inclusion Criteria:

* Male or female 18 years of age or older
* Not a candidate for high-dose chemotherapy and stem cell transplantation (HDT/SCT) due to age, presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT-SCT, or subject preference.
* A Karnofsky Performance Status score of ≥50%
* 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 an asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia (hemoglobin \<10 g/dL), renal function impairment (serum creatinine \> upper limit of normal \[ULN\]) or hypercalcemia (serum calcium \>ULN).
* Must have measurable disease requiring systemic therapy. Measurable disease is defined by at least 1 of the following criteria:

  * Quantifiable serum M-protein value (\>1 g/dL of immunoglobulin (Ig)G or IgM M-protein, \>0.5g/dL of IgA M-protein, \>0.5 g/dL of IgD M-protein)
  * Urine light-chain excretion ≥200 mg/24 hours
* Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

Exclusion Criteria:

* Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum monoclonal protein \<3 g/dL; absence of lytic bone lesions, anemia, 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 immunoglobulin M (IgM) M-protein is present in the absence of a clonal plasma cell infiltration or lytic bone lesions.
* Previously or currently treated with any systemic therapy for multiple myeloma. Prior treatment of hypercalcemia or spinal cord compression with corticosteroids or radiation therapy, respectively, does not disqualify the subject (the dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week period).
* Radiation therapy within 2 weeks before randomization. Enrollment of patients who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
* Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery)
* History of allergy to any of the study medications, their analogues, or excipients in the various formulations
* ≥Grade 2 peripheral neuropathy on clinical examination within 21 days before enrollment.
* Any of the following clinical laboratory values within 21 days prior to enrollment:

  * Absolute neutrophil count (ANC) \<1000 cells/mm\^3
  * Platelets \<100,000 × 10\^9/L, or \<70 × 10\^9/L if thrombocytopenia is considered by the investigator to be due to myeloma infiltration of bone marrow
  * Aspartate aminotransferase \[serum glutamic oxaloacetic transaminase\] (AST \[SGOT\]) or alanine aminotransferase \[serum glutamic-pyruvic transaminase\] (ALT \[SGPT\]) \>2× the upper limit of normal (ULN)
  * Serum creatinine \>2 mg/dL (\>176.8 µmol/L); if the rise in creatinine is related to myeloma and there has been demonstrated a response to hydration, the subject may be enrolled.
* Myocardial infarction within 6 months prior to enrollment or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the investigator. Prior to study entry, any abnormality on electrocardiogram at screening must be determined and documented by the investigator as not medically relevant.
* Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the patient at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical conditions or psychiatric illness likely to interfere with participation in this clinical study.
* Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, or other cancer for which the patient has been disease-free for at least 3 years.
* Female who is pregnant or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test with a sensitivity of at least 50 mIU/mL during Screening.
* Use of any investigational drugs within 30 days before randomization.
C: Inclusion Criteria:

* Age \> 65 year old and not a candidate for stem cell transplant, or younger who refuses or is not eligible for high-dose therapy
* Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage
* Presence of measurable disease
* Karnofsky performance status (PS) \> 60%
* Able to read and complete the HRQOL instruments
* Agrees to use an acceptable barrier method for contraception for the duration of the study
* Pretreatment clinical laboratory values within 14 days of randomization:

platelet count ≥ 100x109/L

* hemoglobin ≥ 8 g/dL
* absolute neutrophil count (ANC) ≥ 1.0x109/L
* AST ≤ 2.5 times the upper limit of normal
* ALT ≤ 2.5 times the upper limit of normal
* total bilirubin ≤ 1.5 times the upper limit of normal
* serum creatinine ≤ 2.5mg/dL
* corrected serum calcium \<14 mg/dL (\<3.5 mmol/L)
* 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.
* Women of child-bearing potential must agree to use 2 methods of contraception: 1 effective (for example hormonal or tubal ligation) and 1 barrier (for example latex condom, diaphragm) for at least 4 weeks before starting the therapy, during the Treatment Period, and for 4 weeks after the last dose;
* Males must agree to use barrier contraception (latex condoms) when engaging in reproductive activity during the Treatment Period and for 4 weeks after the last dose.

Exclusion Criteria:

* Diagnosis of smoldering multiple myeloma or MGUS.
* Diagnosis of Waldenstrom's disease
* Prior or current systemic therapy for multiple myeloma including steroids (with exception of emergency use of a short course \[maximum 4 days\] of steroids before randomization or prior or current use of biphosphonates)
* 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, or to Thalidomide
* Peripheral neuropathy Grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 3.0
* Uncontrolled or severe cardiovascular disease including myocardial infarction 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
* Other malignancy within the past 5 years. Exceptions: basal cell or non metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or FIGO Stage 1 carcinoma of the cervix
* Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes, pulmonary disease) 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.
* Pregnant or lactating women. A serum β-hCG pregnancy test must be performed at the Screening visit, for female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study. Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test with the result obtained 1 day prior to the Baseline visit (or the day of the visit if results are available before drug delivery).
D: Inclusion Criteria:

* Age above 55 years old.
* Diagnosis of MM (Appendix A) and staging (Appendix B), previously untreated.
* Performance status ECOG, 0, 1, or 2 (Appendix C).
* Written informed consent to the study medications and bone marrow biopsy at diagnosis, 12 weeks and 6 months and/or off-study assessment.
* Women who are pregnant or lactating at the time of diagnosis are ineligible. All women of child-bearing potential must have a negative pregnancy test within 24hrs of commencing the thalidomide and must take adequate precautions to prevent pregnancy and should not plan on conceiving children during the treatment program:

  * Adequate precautions are defined as "at least one highly effective method i.e., IUD, hormonal (birth control pills, injections, or implants), tubal ligation, partner's vasectomy AND one additional effective method i.e., latex condom, diaphragm, cervical cap".
  * Women becoming pregnant on protocol will be removed immediately from protocol.
  * Male patients (including patients having had a vasectomy) must use barrier contraception during and for four weeks after completing the thalidomide.
* Patients remain eligible in the presence of abnormal renal function and/or liver function at time of enrollment.
* Absence of severe dementia, able to take medication at home.
* Absence of systemic disorders (gastrointestinal, pulmonary, cardiac and neurological).

Exclusion Criteria:

* Asymptomatic myeloma or solitary plasmacytoma of bone or extramedullary plasmacytoma (without evidence of myeloma).
* Previous or concurrent active malignancies, except surgically removed basal cell carcinoma of the skin or other in situ carcinomas.
* Previous treatment for myeloma, except minimal local radiotherapy to relieve bone pain.
* Other illnesses which would preclude chemotherapy administration or patient compliance.
* Any other serious medical or psychiatric illness which would prevent informed consent.
* Peripheral neuropathy \> NCI criteria grade 2.
* Pregnant or lactating women and patients of childbearing age who refuse to use contraception.
* History of hypersensitivity to thalidomide or any component of the medications.

Answer: C