Please select the eligibility criteria that correspond to the clinical trial below.
Title: Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma Receiving Immunomodulatory Therapy
Brief Summary: Patients living with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE) due to the disease itself and the use of targeted therapies, including immunomodulatory drugs (IMiDs). Prevention of VTE has become a major management challenge during MM treatment. There is a paucity of data with respect to the non-vitamin K oral anticoagulants (NOACs) in the cancer population. However, the NOACs offer comparable efficacy but improved safety compared with warfarin. Apixaban has shown excellent safety and efficacy for treatment and prevention of recurrent VTE (1,2). The safety and efficacy of apixaban for primary prevention of VTE in MM patients has not been established.

Aim #1: To quantify the 6-month rate of major and clinically relevant non-major bleeding in MM patients receiving IMiDs who are prescribed apixaban 2.5 mg orally twice daily for primary prevention of VTE.

Hypothesis #1: The 6-month rate of major and clinically relevant non-major bleeding in MM patients receiving IMiDs who are prescribed apixaban 2.5 mg orally twice daily for primary prevention of VTE will be ≤3% (2). Although the MM population, in general, has a higher medical acuity than that of the previous large randomized controlled trials of apixaban, we will be selecting a stable population of MM patients who are appropriate for immunomodulatory therapy.

Aim #2: To quantify 6-month rate of symptomatic VTE in MM patients receiving IMiDs who are prescribed apixaban 2.5 mg orally twice daily for primary prevention of VTE.

Hypothesis #2: The 6-month rate of symptomatic VTE in MM patients receiving IMiDs who are prescribed apixaban 2.5 mg orally twice daily for primary prevention of VTE will be \<7% (3). Although additional therapies for MM such as dexamethasone and erythropoietin-stimulating agents may further increase the risk of VTE, the rate of incident VTE should be reduced to \<7% with apixaban.


Options:
A: Inclusion Criteria:

* Men and women
* Age \> 18 years
* Current or prior diagnosis of symptomatic MM based on International Myeloma Working Group (IMWG) guidelines (http://imwg.myeloma.org/category/guidelines-2/) and will be starting or already receiving IMiD therapy with thalidomide \[Thalomid\], lenalinomide \[Revlimid\], or pomalidomide \[Pomalyst\]
* IMiD therapy given in the setting of newly diagnosed MM, relapsed MM, progressive MM, maintenance therapy or consolidation therapy as per IMWG criteria
* Willing to provide written informed consent
* Eastern Cooperative Oncology Group (ECOG) functional status ≤ 2
* Providers must plan to treat the patient with IMiD therapy for a minimum of 6 cycles

Exclusion Criteria:

* Pregnancy
* Breastfeeding
* Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control (such as oral contraceptives, other hormonal contraceptives \[vaginal products, skin patches, or implanted or injectable products\], or mechanical products such as an intrauterine device or barrier methods \[diaphragm, condoms, spermicides\]) to avoid pregnancy for the entire study
* Any prior venous thromboembolism
* Contraindication to anticoagulant therapy
* Conditions for which serious bleeding may occur including:

  1. Current or within last 6 months: intracranial bleeding, intraocular bleeding, gastrointestinal bleeding, endoscopically documented ulcer disease
  2. Current or within last month: head trauma or other major trauma, major surgery
  3. Current or within last 2 weeks: stroke, neurosurgical procedure
  4. Current: gross hematuria, major unhealed wound, major surgery planned during the trial period, intracranial mass, vascular malformation, or aneurysm, overt bleeding, blood dyscrasia
  5. CNS involvement of MM or other history of CNS malignancy
* Active and clinically significant liver disease
* Uncontrolled hypertension: systolic blood pressure \>180 mm Hg or diastolic blood pressure \>100 mm Hg
* Current endocarditis
* Requirement for ongoing anticoagulant therapy, including mechanical heart valve replacement and atrial fibrillation
* Severe valvular heart disease, including rheumatic heart disease and mitral stenosis
* Bioprosthetic heart valve replacement
* Requirement for dual antiplatelet therapy or single agent antiplatelet therapy with clopidogrel, prasugrel, or ticagrelor
* Requirement for aspirin at a dose higher than 165 mg daily.
* Hemoglobin \< 9 mg/dL at time of screening
* Platelet count \< 100,000/mm3 at time of screening
* Serum calculated creatinine clearance (CrCl) \< 25 ml/m at time of screening
* Alanine aminotransferase or aspartate aminotransferase level \> 2 times the upper limit of the normal at time of screening
* Total bilirubin level \> 1.5 times the upper limit of the normal at time of screening
* Life expectancy \< 12 months or hospice care
* Prisoners or subjects who are involuntarily incarcerated
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
* Receiving concurrent non-FDA-approved or investigational agents or has received an investigational agent within the past 30 days prior to the first dose of study treatment (with the exception of approved medications being used for an approved indication, e.g., investigating a new dosing regimen for an approved indication).
* Any condition, which in the opinion of the investigator, would put the subject at an unacceptable risk from participating in the study
* Any other medical, social, logistical, or psychological reason, which in the opinion of the investigator, would preclude compliance with, or successful completion of, the study protocol
B: 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
C: Inclusion Criteria:

Patients must meet all of the following criteria to be considered for enrolment:

* Women with newly diagnosed, histologically proven EOC are potentially eligible. Patients with primary peritoneal or fallopian tube tumours of equivalent histology are also considered for enrolment. If open or true cut biopsy is not available, fine needle aspiration (FNA) showing an adenocarcinoma is considered diagnostic for EOC if all 4 (a to d) of the following conditions are satisfied:

  1. Patient has a pelvic mass, AND
  2. Any evidence of disease larger than 1 cm in the upper abdomen (unless proven stage IV), AND
  3. Normal mammography within 6 weeks of randomization, AND
  4. Serum CA-125/CEA greater than or equal to 25. If the ratio is less than 25, a barium enema (or colonoscopy) and gastroscopy (or radiological examination of the stomach) must be negative for a primary tumour.
* Between the ages of 18 and 75.
* FIGO stage IIB to IV disease.
* A pre-study CA-125 level at least twice the upper limit of normal.
* Eligible for standard adjuvant treatment with taxane- and platinum-based chemotherapy by meeting all of the following laboratory findings within 7 days prior to randomization:

  1. Absolute granulocyte count of at least 1.5 x 10 9/L (1500 per cubic millimetre).
  2. Platelet count of at least 150 x 109/L (100,000 per cubic millimetre).
  3. Serum creatinine no greater than 177 micromol/L (2.0 mg/dL).
  4. Total bilirubin level no greater than 1.5 times the upper limit of normal at the local centre.
  5. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels no greater than 3 times the upper limit of normal of the local centre.

Exclusion Criteria:

* Borderline ovarian tumours.
* Received prior chemotherapy or radiation therapy for EOC.
* Received mouse antibodies anytime during the 28 days prior to the pre-study CA-125 level.
* History of another malignancy, unless disease-free for 5 years or greater; non-melanomatous skin carcinoma or curatively treated carcinoma-in-situ of the cervix are excepted.
* Eastern Cooperative Oncology Group (ECOG) performance score of 3 or 4.
* Life expectancy less than 12 weeks.
* Complete bowel obstruction at the time of study enrolment.
* Receiving long-term anticoagulant therapy for an established indication (e.g., atrial fibrillation, mechanical heart valves).
* Bleeding diathesis (e.g., evidence of DIC, hereditary or acquired bleeding disorder).
* History of allergy to any heparin (e.g., heparin-induced thrombocytopenia).
* Significant cardiac history including myocardial infarction within preceding 6 months, congestive heart failure, clinically relevant atrial or ventricular arrhythmias, history of 2nd or 3rd degree heart blocks unless pacemaker is implanted.
* Serious medical conditions that preclude the administration of chemotherapy, anticoagulant therapy, or adherence to protocol, including but not exclusive to:

  1. Allergic reactions to drugs containing cremophor or compounds chemically related to taxanes or platinum analogues.
  2. Significant neurologic or psychiatric disorder that would impair obtaining informed consent and reliable follow-up.
  3. Uncontrolled hypertension despite optimal medical therapy.
  4. Active, uncontrolled infection.
* Women who are pregnant or lactating or are of childbearing potential but are not using effective contraception.
* Total body weight of less than 40 kg.
* Concurrent treatment with experimental or investigational drugs.
* Unable or unwilling to attend scheduled follow-ups.
* Unable (e.g., language barrier, mental illness) to provide informed consent.
D: Inclusion Criteria:

* Have histologically confirmed solid malignancy including but not limited to: pancreas, lung, stomach, colon, rectum, bladder, breast, ovary, renal or lymphoma (hematologic), with locally advanced or metastatic disease
* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* Have a Khorana thromboembolic risk Score greater than or equal to (\>=) 2
* Creatinine clearance (CrCl) \>= 30 milliliter per minute (mL/min)
* Plan to initiate systemic cancer therapy within plus or minus (+-) 1 week of receiving the first dose of study drug with the intention of receiving systemic cancer therapy during the double-blind treatment period for an intended duration determined by the treating oncologist according to standard protocols of clinical care

Exclusion Criteria:

* Diagnosis of primary brain tumors
* Known history of brain metastases
* Bleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleeding
* Hematologic malignancies with the exception of lymphoma
* Platelet count less than (\<) 50,000/millimeter\^3 (mm\^3), Life expectancy of less than or equal to (\<=) 6 months

Answer: A