Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Intergroup Multicentre, Randomized, Controlled 3 Arm Parallel Group Study to Determine the Efficacy and Safety of Lenalidomide in Combination With Dexamethasone (RD) Versus Melphalan, Prednisone and Lenalidomide (MPR) Versus Cyclophosphamide, Prednisone and Lenalidomide (CPR) in Newly Diagnosed Elderly Multiple Myeloma Subjects
Brief Summary: This is a multicenter, randomized, controlled, 3 arm parallel group study designed to evaluate the efficacy and safety of three all-oral combinations: lenalidomide with dexamethasone (Rd) in comparison with lenalidomide in association with MP (MPR) and lenalidomide in association with cyclophosphamide - prednisone (CPR) in newly diagnosed symptomatic MM patients. This protocol also provides a substudy designed to observe asymptomatic patients excluded to the protocol that in any case could be inserted in the study.


Options:
A: Inclusion Criteria:

* Active Multiple Myeloma Stage II or III Durie Salmon
* Measurable levels of myeloma paraprotein in serum (≥1.0g/dL) or urine (≥ 0.2g excreted in a 24-hour collection sample)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2
* Women of child bearing potential must agree to abstain for heterosexual intercourse or use 2 methods of contraception, one effective (for example hormonal or tubal ligation) and one barrier (for example latex condom, diaphragm)
* Males must agree to use barrier contraception (latex condoms) when engaging in reproductive activity

Exclusion Criteria:

* Pregnant or lactating females
* Peripheral neuropathy ≥ to grade 2 of the NCI CTC.
* Prior history of malignancy unless subject has been free of disease for ≥ 3 years
* Lab abnormality: Absolute neutrophil count (ANC) \<1,000 cells/mm\^3 (1.0 x 10\^9/L)
* Lab abnormality: Platelet count \<50,000/mm\^3 (50.0 x 10\^9/L)
* Lab abnormality: Serum creatinine \>3.0 mg/dL (265 µmol/L)
* Lab abnormality: Serum glutamic oxaloacetic transaminase (SGOT) /Aspartate aminotransferase (AST) or Serum glutamic pyruvic transaminase (SGPT)/Alanine transaminase (ALT) \>3.0 x upper limit of normal (ULN)
* Lab abnormality: Serum total bilirubin \> 2.0 mg/dL (34 µmol/L)
B: Inclusion Criteria:

* Participant must have documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable secretory disease, as assessed by the central laboratory, and defined in protocol
* Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age \>=65 years, or in participants \<65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation
* Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
* Meet the clinical laboratory criteria as specified in the protocol
* A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization
* Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal \[birth control pills, injections, hormonal patches, vaginal rings or implants\] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy

Exclusion Criteria:

* Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma
* Participant has a diagnosis of Waldenstrom'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
* Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment
* Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4
* Participant has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
* Participant has had radiation therapy within 14 days of randomization
* Participant has had plasmapheresis within 28 days of randomization
* Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal), known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma is allowed)
* Participants with known or suspected COPD must have a FEV1 test during screening
* Participant is known to be seropositive for human immunodeficiency virus (HIV), known to have hepatitis B surface antigen positivity, or history of to have a history of hepatitis C
* Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
C: Inclusion Criteria:

* Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
* Patient has given voluntary written informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* Patient is 65 years old or older at the time of signing the informed consent or younger patients not candidate to high dose therapy
* Female patient is either post-menopausal or surgically sterilized or, if at child-bearing potential†, must:

  * understand that the study medication could have an expected teratogenic risk
  * Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception\*
* Implant\*\*
* Levonorgestrel-releasing intrauterine system (IUS)\*\*
* Medroxyprogesterone acetate depot
* Tubal sterilisation
* Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses
* Ovulation inhibitory progesterone-only pills (i.e., desogestrel)

Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception.

* prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection

  * Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
  * Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence

    - Male subjects must
  * Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
  * Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.

    - All subjects must
  * Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
  * Agree not to share study medication with another person and to return all unused study drug to the investigator.

    - Patient was previously diagnosed with symptomatic MM based on standard criteria, and has measurable disease, defined as follows:
  * Secretory myeloma: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of \>200 mg/24 hours;
  * Non-secretory myeloma: \> 30% plasma cells in the bone marrow and at least one plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan).

    * Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized within each country.
    * Patient has a Karnofsky performance status _ 60%.
    * Patient has a life-expectancy \> 6 months
    * Patients must have a adequate cardiac function
    * Patients must have adequate pulmonary function
    * Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1):
    * Platelet count ≥ 75 x 109/L without transfusion support within 7 days before the test.
    * Absolute neutrophil count (ANC) ≥1.0 x 109/L without the use of growth factors.
    * Corrected serum calcium ≤14 mg/dL (3.5 mmol/L).
    * Aspartate transaminase (AST): ≤2.5 x the upper limit of normal (ULN).
    * Alanine transaminase (ALT): ≤ 2.5 x the ULN.
    * Total bilirubin: ≤1.5 x the ULN.
    * Calculated or measured creatinine clearance: ≥30 mL/minute

Exclusion Criteria:

* Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; \< to the equivalent of dexamethasone 40 mg/day for 4 days).
* Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
* Pregnant or lactating females.
* Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥3 years. Exceptions include the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
D: Inclusion Criteria:

* Stage II or III multiple myeloma according to Durie and Salmon criteria.
* Patients between 65 and 75 years of age
* Previously untreated patients

Exclusion Criteria:

* Prior history of another neoplasm (except basocellular cutaneous or cervical epithelioma)
* Primary or associated amyloidosis
* World Health organisation performance index of at least 3
* Significant renal insufficiency with creatinine serum levels of 5.0 mg per deciliter or more
* Cardiac or hepatic dysfunction
* Cerebral circulatory insufficiency
* Absolute contraindication to corticosteroids
* Peripheral neuropathy
* HIV or hepatitis B or C positivity
* Patients who had geographic, social or psychological conditions which might prevent adequate follow-up

Answer: C