Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma

Gregory Piazza

Status and phase

Completed

Phase 4

Conditions

Venous Thromboembolism

Multiple Myeloma

Treatments

Drug: Apixaban

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02958969

18-493

Details and patient eligibility

About

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.

Full description

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.

Enrollment

50 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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