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:

1. Hospitalized medical patients 70 years of age or older
2. Acute medical illness with significant decrease in mobility expected for at least 4 days (patient bedridden or only able to walk short distances)
3. written informed consent

Exclusion Criteria:

1. immobilization longer than 3 days prior to randomization
2. prior major surgery, trauma or invasive procedure within the last 4 weeks including any injuries or operation of central nervous system
3. expected major surgical or invasive procedure within the next 3 weeks after randomization
4. LMWH/heparin administration longer than 48 hours in the 5 days prior to randomization
5. immobilization due to cast or fracture
6. indication for anticoagulatory or thrombolytic therapy
7. acute symptomatic DVT / PE
8. known hypersensitivity to any of the study drugs or drugs with similar chemical structures
9. Acute or history of heparin induced thrombocytopenia type II (HIT II)

Other protocol-defined inclusion/exclusion criteria may apply
B: Inclusion Criteria:

* A histologic diagnosis of malignancy;
* At planned initiation of a new systemic chemotherapy regimen (including patients starting on first chemotherapy or patients previously treated but starting on a new regimen);
* A risk score for VTE ≥3 \[assign score of 2 for very high risk sites of cancer (stomach, pancreas), score of 1 for high risk site (lung, lymphoma, gynecologic, bladder, testicular) and score of 0 for all other sites\], hemoglobin \<10 g/dL or planned use of erythropoiesis stimulating agents, platelet count ≥350,000/mm3, total leukocyte count \> 11,000/mm3 or body mass index ≥ 35 kg/m2\]. Any counts meeting criteria drawn within 2 weeks prior to enrollment are considered acceptable.
* Age 18 years or older
* Provide written, informed consent.

Exclusion Criteria:

* Active bleeding or at high risk of serious bleeding complication in the opinion of the investigator
* Diagnosis of primary brain tumor multiple myeloma, leukemia, or myelodysplastic syndrome
* Planned stem cell transplant
* Life expectancy \< 6 months
* Known allergy to heparin or LMWH
* Patient or caregiver incapable of daily self-injection
* Acute or chronic renal insufficiency with creatinine clearance \< 30 mL/min
* History of heparin-induced thrombocytopenia
* Allergy to contrast agents
* Pregnancy
* Need for anticoagulant therapy
* Platelet count \< 75,000/mm3
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 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.
D: 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.

Answer: C