Please select the eligibility criteria that correspond to the clinical trial below.
Title: A PHASE 3, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF LENALIDOMIDE, MELPHALAN AND PREDNISONE (MPR) Versus MELPHALAN (200 mg/m2) FOLLOWED BY STEM CELL TRANSPLANT IN NEWLY DIAGNOSED MULTIPLE MYELOMA SUBJECTS
Brief Summary: To compare the efficacy of the combination of lenalidomide with low-dose melphalan versus high-dose melphalan in newly diagnosed, symptomatic MM patients.


Options:
A: Inclusion Criteria:

* Male or female subjects older than the minimum legal adult age (country specific);
* Acute symptomatic proximal DVT and/or symptomatic PE confirmed at the site by appropriate diagnostic imaging;
* Able to provide written informed consent

Exclusion Criteria:

* thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE;
* More than 48 hours pre-treatment with anticoagulant therapy prior to randomization;
* Calculated Creatinine clearance (CrCL) \< 30 mL/min;
* significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis) or alanine transaminase (ALT) \>\\= 2 times the upper limit of normal (ULN), or total bilirubin (TBL) x 1.5 times the ULN;
* patients with active cancer for whom long term treatment with (LMW) heparin is anticipated;
* active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin or warfarin;
* chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs);
* treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet therapy;
* concurrent treatment with potent P-gp inhibitors;
* subjects with any condition that, as judged by the investigator, would place the subject at increased risk of harm if he/she participated in the study
B: Inclusion Criteria:

* Patients with a diagnosis of active cancer.
* Symptomatic and objectively confirmed VTE.
* ≥ 18 years of age or above the legal age of consent as per country specific regulations.
* Patients with Eastern Co-operative Oncology Group (ECOG) performance status of 0, 1 or 2.
* Signed informed consent.

Exclusion Criteria:

* Life expectancy \< 6 months.
* Patients with basal cell carcinoma or non-melanoma skin cancer.
* Creatinine clearance ≤ 20 ml/min.
* Contra-indications to anticoagulation.
* Known hypersensitivity to the investigational product (Innohep®) or the reference product (warfarin).
* History of heparin-induced thrombocytopenia (HIT).
* Pre-randomisation therapeutic anticoagulant treatment for acute VTE administered for more than 72 hours prior to randomisation.
* Patients unlikely to comply with the protocol.
* Participation in another interventional study.
* Pregnant or breast-feeding women.
* Women of childbearing potential.
C: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreas

  * Patients with clinical 'high probability' of pancreatic cancer and biopsy suggestive but not diagnostic of pancreatic cancer may be eligible based on review by the principal investigator
* Measurable or evaluable disease
* No clinical evidence of active venous thromboembolism

PATIENT CHARACTERISTICS:

* Karnofsky performance status (PS) 60-100% OR WHO PS 0-2
* Life expectancy \> 12 weeks
* Absolute neutrophil count \> 2,000/mm³
* WBC \> 3,000/mm³
* Platelet count \> 100,000/mm³
* Creatinine clearance \> 50 mL/min
* INR ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin \< 1.5 times ULN (stent allowed)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No cerebrovascular accident within the past 6 months
* No obvious contraindication to anticoagulation, including the following:

  * Bleeding diathesis
  * Active peptic ulcer
  * Ulcerating cancer into duodenum
* No history of other advanced malignancy
* No gross hematuria
* No melaena or gross evidence of gastrointestinal bleeding (other than piles)
* No requirement for a central line
* No other significant medial or psychiatric illness that, in the opinion of the investigator, would preclude study participation

PRIOR CONCURRENT THERAPY:

* No prior gemcitabine hydrochloride-containing treatment
* No other concurrent cytotoxic chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), or experimental medications
* No other concurrent specific anticancer therapy as a result of disease progression
* No concurrent caval filter device
* No other concurrent anticoagulants for venous thromboembolism or other reasons (e.g., atrial fibrillation)
* No concurrent acetylsalicylic acid (\> 75 mg) as an antiplatelet drug for a preexisting cardiovascular condition
* No concurrent clopidogrel bisulfate
D: 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 younger at the time of signing the informed consent
* Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable double method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
* Negative serum β-human chorionic gonadotropin ( β-HCG) pregnancy test both 24 hours prior to beginning of therapy and then at 4 weeks intervals in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles during study treatment for subjects of childbearing potential
* Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of lenalidomide therapy.
* Patient was diagnosed with symptomatic multiple myeloma based on standard criteria (9), and has measurable disease, defined as follows: 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; measurable plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan); bone marrow plasma cells\>10%.
* Patient has a Karnofsky performance status ≥ 60%.
* Patient has a life-expectancy \> 6 months
* Patient has not active infectious hepatitis type B or C, and has HIV negative test
* Patients must have an ejection fraction by ECHO or MUGA \> 50% performed within 60 days prior to registration
* Patients must have adequate pulmonary function studies \> 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) \> 50% of predicted. Patients unable to complete pulmonary function tests because of myeloma-related chest pain, must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.
* 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) ≥ 1.5 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
* Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized within each country.

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)
* Neuropathy of ≥ grade 2 severity.
* Patients previously diagnosed as bearing deep venous thrombosis or arterial thromboembolic event within the latest 12 months, or bearing a clear indication for anti-platelet or anticoagulant therapy or bearing a high risk of bleeding complications are ineligible for the sub-study protocol.

Answer: D