Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label, Single-arm, Phase 2 Study of Carfilzomib in Patients With Relapsed and Refractory Multiple Myeloma
Brief Summary: To evaluate the overall response rate and safety and tolerability of carfilzomib in subjects with relapsed and refractory multiple myeloma.

Patients must have received prior treatment with bortezomib and either thalidomide or lenalidomide and be refractory to their last treatment.


Options:
A: Inclusion Criteria:

* Patients with multiple myeloma who have received at least 1 prior therapy and who have either responded and later had progressive disease or have progressed during their first therapy (primary refractory) are eligible for the study
* Patients who may have received prior doxorubicin but not more than a cumulative dose of 240 milligram per meter square (mg/m\^2) doxorubicin, DOXIL, or the equivalent amount of another anthracycline (i.e., 1 mg doxorubicin = 1 mg DOXIL/CAELYX = 1.8 mg epirubicin = 0.3 mg mitoxantrone = 0.25 mg idarubicin)
* Must have normal cardiac function, as evidenced by a left LVEF within institutional normal limits.

Exclusion Criteria:

* History of treatment with VELCADE or progressive disease while receiving an anthracycline-containing regimen
* No change in disease status during initial therapy
* No treatment for malignancy within past 5 yrs (other than multiple myeloma) or progressive disease while receiving anthracycline-containing regimen
* Non-secretory disease
* Myocardial infarct within past 6 months
* No major surgery in past 30 days.
B: 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before performance of any study-related procedure not part of normal medical care, with the understanding it can be withdrawn at any time without prejudice to future medical care.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.
C: Inclusion Criteria:

* Disease Related

  * Multiple myeloma
  * Subjects must have measurable disease defined as one of the following:

    * Serum M-protein ≥ 1 g/dL
    * Urine M-protein ≥ 200 mg/24 hours
    * Serum FLC ≥ 10 mg/dL with abnormal ratio (A0 Only)
    * Quantitative immunoglobulin levels using nephelometry or turbidometry (only if protein electrophoresis was felt to be unreliable for M-protein measurement) (A0 Only)
  * Subjects must have been responsive (i.e., achieved an MR or better) to first-line, standard of care therapy
  * Refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy.
  * Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction therapy and stem cell transplant will be considered as one regimen (A1 Only)
  * Subjects must have received prior treatment with bortezomib, and either thalidomide or lenalidomide
  * Subjects must have received an alkylating agent either alone or in combination with other myeloma treatments (history of stem cell transplant is acceptable) (A1 Only)
  * Subjects must have received an anthracycline either alone or in combination with other myeloma treatments, unless not clinically indicated (A1 Only)
* Demographic

  * Males and females \> 18 years of age
  * Life expectancy of more than three months
  * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* Laboratory

  * Adequate hepatic function, with bilirubin less than 2.0 times the upper limit of normal, and AST and ALT of less than 3.0 times the upper limit of normal
  * Uric acid within normal range (A0 Only)
  * Total white blood cell (WBC) count ≥ 2.0 × 109/L, absolute neutrophil count (ANC) ≥ 1.0 × 109/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50.0 × 109/L (A0 Only)
  * Absolute neutrophil count \> 1,000/mm3, hemoglobin \> 8.0 g/dL, and platelet count \> 50,000/mm3 (A1 Only)

    * Subjects should be platelet transfusion independent
    * Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks
    * Subjects may receive red blood cell (RBC) or platelet transfusions or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines
  * Calculated and measured creatinine clearance of ≥ 30 mL/minute, calculated using the formula of Cockcroft and Gault \[(140 - Age) X Mass (kg) / (72 X Creatinine mg/dL)\]. Multiply result by 0.85 if female.
* Ethical / Other

  * Written informed consent in accordance with federal, local, and institutional guidelines
  * Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. Post menopausal females (\> 45 years old and without menses for \> 1 year) and surgically sterilized females are exempt from a pregnancy test. Male subjects must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential.

Exclusion Criteria:

* Disease Related

  * Multiple Myeloma IgM (A1 Only)
  * Subjects who failed to achieve at least a confirmed MR(≥ 25% reduction in M-protein for ≥ 6 weeks) (A1 Only)
  * Subjects with non-secretory multiple myeloma, defined as \< 1 g/dL M-protein in serum and \< 200 mg/24 hr M-protein in urine
  * Subjects with disease measurable only by serum free light chain (SFLC) analysis (A1 Only)
  * Glucocorticoid therapy (prednisone \> 10 mg/day orally or equivalent) within the last three weeks
  * POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  * Plasma cell leukemia
  * Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the three weeks prior to first dose
  * Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose
  * Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to Day 1, whichever time is greater
  * Prior treatment with carfilzomib
* Concurrent Conditions

  * Major surgery within three weeks before Day 1
  * Congestive heart failure (New York Heart Association class III to IV), symptomatic cardiac ischemia, cardiomyopathy, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months, LVEF \< 40
  * Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose
  * Known or suspected HIV infection or subjects who are HIV seropositive
  * Active hepatitis A,B,or C infection
  * Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer \<Gleason Grade 6 with stable PSA
  * Subjects with treatment related myelodysplastic syndrome
  * Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study initiation
  * Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac or renal impairment (A1 Only)
  * Subjects with known or suspected amyloidosis (A1 Only)
  * Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis (A1 Only)
  * Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent (A1 Only)
* Ethical / Other

  * Female subjects who are pregnant or lactating
  * Serious psychiatric or medical conditions that could interfere with treatment
D: 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

Answer: C