Please select the eligibility criteria that correspond to the clinical trial below.
Title: International, Multi-center, Prospective, Double Randomized, Open Phase III Study Evaluating Thalidomide/Dexamethasone Versus Melphalan/Prednisone as Induction Therapy and Thalidomide/Interferon-alpha Versus Interferon-alpha as Maintenance Therapy in Newly Diagnosed Patients With Multiple Myeloma
Brief Summary: This is an international multi-center prospective, double randomized, open, controlled phase III study with a phase II entrance phase to compare the therapeutic efficacy of thalidomide plus dexamethasone to conventional melphalan plus prednisone in newly diagnosed myeloma patients.


Options:
A: 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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.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.
B: Inclusion Criteria:

1. Must understand and voluntarily sign informed consent form
2. Age ≥ 18 years at the time of signing consent
3. Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:

   * MM diagnostic criteria (all 3 required):
   * Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma
   * Monoclonal protein present in the serum and/or urine
   * Myeloma-related organ dysfunction (at least one of the following) \[C\] Calcium elevation in the blood (serum calcium \>10.5 mg/dl or upper limit of normal) \[R\] Renal insufficiency (serum creatinine \>2 mg/dl) \[A\] Anemia (hemoglobin \<10 g/dl or 2 g \< laboratory normal) \[B\] Lytic bone lesions or osteoporosis

   AND have measurable disease by protein electrophoresis analyses as defined by the following:
   * IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours
   * IgA multiple myeloma: Serum M-protein level ≥ 0.5 g/dl or urine M-protein level ≥ 200 mg/24 hours
   * IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200mg/24hours
   * IgD multiple myeloma: Serum M-protein level ≥ 0.05 g/dl or urine M-protein level ≥ 200 mg/24 hours
   * Light chain multiple myeloma: Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours

   AND are at least 65 years of age or older or, if younger than 65 years of age, are not candidates for stem cell transplantation because:
   * The patient declines to undergo stem cell transplantation or
   * Stem cell transplantation is not available to the patient due to cost or other reasons
4. ECOG performance status of 0, 1, or 2
5. Able to adhere to the study visit schedule and other protocol requirements
6. Females of child-bearing potential (FCBP)\^2:

   1. Must agree to undergo two medically supervised pregnancy tests prior to starting study therapy with either Rd or MPT. The first pregnancy test will be performed within 10-14 days prior to the start of Rd or MPT and the second pregnancy test will be performed within 24 hours prior to the start of Rd or MPT. She must also agree to ongoing pregnancy testing during the course of the study and after the end of study therapy. This applies even if the patient practices complete and continued sexual abstinence.
   2. Must commit to either continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy.
7. Male Patients:

   1. Must agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy.
   2. Must agree to not donate semen during study drug therapy and for a period after end of study drug therapy.
   3. Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.
8. All patients must:

   1. Have an understanding that the study drug could have a potential teratogenic risk.
   2. Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
   3. Agree not to share study medication with another person. All FCBP and male patients must be counseled about pregnancy precautions and risks of fetal exposure.

Exclusion Criteria:

1. Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid \[i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of randomization\]).
2. Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, patient with unstable cardiac disease as defined by: Cardiac events such as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; patients with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
3. Pregnant or lactating females.
4. Any of the following laboratory abnormalities:

   * Absolute neutrophil count (ANC) \< 1,000/µL (1.0 x 109/L)
   * Untransfused platelet count \< 50,000 cells/µL (50 x 10\^9/L)
   * Serum SGOT/AST or SGPT/ALT \> 3.0 x upper limit of normal (ULN)
5. Renal failure requiring hemodialysis or peritoneal dialysis.
6. Prior history of malignancies, other than multiple myeloma, unless the patient 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 histological finding of prostate cancer (TNM stage of T1a or T1b)
7. Patients who are unable or unwilling to undergo antithrombotic therapy.
8. Peripheral neuropathy of \> grade 2 severity.
9. Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.

   * 1 A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to be myeloma-related.
   * 2 A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (i.e., amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
C: Inclusion Criteria:

* Patients with Multiple Myeloma of IgG, IgA, IgD, IgE, IgM lambda or kappa light chain, low secretory or non-secretory disease
* WHO performance status 0,1,2,or 3
* No prior treatment of multiple myeloma
* Clear requirement of treatment (usually Durie/Salmon stage II or III)
* Anticipated life expectancy of at least 3 months
* Adequate organ function
* Minimum recovery period of 2 weeks following any major surgical procedure before entry into this study
* Women, who are sterilized via hysterectomy or bilateral tubal ligation or at least one year post-menopausal
* Age of at least 19 years, there is no upper age limit patients must have been informed and must have signed an informed consent

Exclusion Criteria:

* Extramedullary plasmocytoma or solitary plasmocytoma without evidence of dissemination of disease
* Benign monoclonal gammopathy
* Multiple myeloma of IgM without osteolytic bone lesions
* Smouldering myeloma
* More than 3 irradiation fields
* Irreversible performance status of WHO4
* Prior treatment of myeloma with any of the following: chemotherapeutic or immunomodulatory agents, corticosteroids, antiangiogenic agents or other investigational drugs
* Women of childbearing potential
* Preexisting peripheral polyneuropathy
* Congestive heart failure NYHA III, IV
* Acute infection requiring systemic antibiotics at study entry until resolved
* Any uncontrolled underlying medical condition (eg diabetes, glaucoma)
* Second primary malignancy (with the exception of cervical carcinoma in situ and non-myeloma skin malignancies) unless patient has been disease-free for at least three years
D: 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

Answer: C