Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma Receiving Immunomodulatory Therapy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Frequency of Major and Clinically Relevant Non-major Bleeding
研究概览
简要总结
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.
详细描述
MM is associated with an increased risk of venous thromboembolism (VTE). The use of targeted therapies, including immunomodulatory drugs (IMiDs), has improved outcomes for patients with MM but also increases the risk of VTE. Prevention of VTE has become a major management dilemma during MM treatment. There is a paucity of data with respect to the non-vitamin K oral anticoagulants (NOACs) in the cancer population, including patients with MM. However, the NOACs have been shown to 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). Compared with injectable thromboprophylactic regimens such as enoxaparin, apixaban offers the advantages of being orally administered and less reliant on renal clearance. The safety and efficacy of apixaban for primary prevention of VTE in MM patients has not been established. The current study will evaluate apixaban (2.5 mg twice daily) in a patient population without a history of prior VTE. Although the current study population is high risk for VTE, it is likely to be lower risk for VTE than those of the prior randomized controlled trials of apixaban for secondary prevention. Furthermore, current practice is to provide MM patients receiving IMiDs with prophylactic doses (not treatment doses) of low-molecular weight heparin (such as enoxaparin 40 mg injected daily). Accordingly, the rationale to test apixaban (2.5 mg twice daily) is consistent with the standard practice of prophylactic anticoagulation.
The current study will provide event rates that will inform the design of a larger randomized controlled trial. If safe and effective, apixaban will satisfy a critical unmet need and will represent a substantial advance and "game changer" in the prevention of VTE in this high risk patient population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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:
- •Current or within last 6 months: intracranial bleeding, intraocular bleeding, gastrointestinal bleeding, endoscopically documented ulcer disease
- •Current or within last month: head trauma or other major trauma, major surgery
- •Current or within last 2 weeks: stroke, neurosurgical procedure
- •Current: gross hematuria, major unhealed wound, major surgery planned during the trial period, intracranial mass, vascular malformation, or aneurysm, overt bleeding, blood dyscrasia
- •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
研究组 & 干预措施
Apixaban
apixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months
干预措施: Apixaban (Drug)
结局指标
主要结局
Frequency of Major and Clinically Relevant Non-major Bleeding
时间窗: 6 months
Major and clinically relevant non-major bleeding. Using the ISTH classification, bleeding is defined as major if it is overt and associated with a decrease in the hemoglobin level of 2 g/dL or more, requires the transfusion of 2 or more units of blood, occurs into a critical site, or contributes to death (12). Using the ISTH classification, clinically relevant nonmajor bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, surgical intervention, or interruption of the study drug.
Frequency of Symptomatic Venous Thromboembolism
时间窗: 6 months
Symptomatic deep vein thrombosis or pulmonary embolism
次要结局
- Frequency of All-cause Mortality(6 months)
- Frequency of Atherothrombotic Events(6 months)
研究者
Gregory Piazza
Sponsor Investigator
Brigham and Women's Hospital