Venous ThromboembolismPhase 4NCT02958969
Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
A Phase 4 study testing Apixaban in people with Venous Thromboembolism and Multiple Myeloma, run by Gregory Piazza at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism, Multiple Myeloma
- What is being tested?
- Apixaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Feb 2018to 19 Nov 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 30Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma Receiving Immunomodulatory Therapy
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.
Read more
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.
Read the detailed 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.
- Conditions
- Venous Thromboembolism, Multiple Myeloma
- Being tested
- Apixaban
- Keywords
- venous thromboembolism, multiple myeloma, anticoagulation
- Medical subject headings
- Venous Thromboembolism, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Thromboprophylaxis
apixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Experimental | apixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months Receives: Drug: Apixaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Symptomatic Venous Thromboembolism
Symptomatic deep vein thrombosis or pulmonary embolism
Measured: 6 months
Frequency of Major and Clinically Relevant Non-major Bleeding
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.
Measured: 6 months
Secondary outcomes (2)
Frequency of All-cause Mortality
All-cause mortality at 6 months will be recorded. Cause of death will be classified as related to cancer, myocardial infarction, PE, other cardiovascular or other disease state. Death will be attributed to PE if there is evidence to support an association with PE.
Measured: 6 months
Frequency of Atherothrombotic Events
6-month rates of myocardial infarction and stroke will be calculated.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2016 (estimated)
- Study start28 Feb 2018
- Primary completion30 Jun 2019
- Study completion19 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gregory Piazza
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Gregory Piazza, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02958969
- Sponsor's protocol ID
- 18-493
- Status last verified
- Dec 2019
- First submitted
- 5 Nov 2016
- Last updated
- 17 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kahale LA, Matar CF, Tsolakian I, Hakoum MB, Yosuico VE, Terrenato I, Sperati F, Barba M, Hicks LK, Schunemann H, Akl EA. Antithrombotic therapy for ambulatory patients with multiple myeloma receiving immunomodulatory agents. Cochrane Database Syst Rev. 2021 Sep 28;9(9):CD014739. doi: 10.1002/14651858.CD014739.
PubMed 34582035
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma Receiving Immunomodulatory Therapy
- ClinicalTrials.gov ID
- NCT02958969
- Acronym / sponsor ID
- 18-493
- Conditions
- Venous Thromboembolism, Multiple Myeloma
- Keywords
- venous thromboembolism, multiple myeloma, anticoagulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Gregory PiazzaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 28 Feb 2018 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 19 Nov 2019 (actual)
- First posted
- 8 Nov 2016 (estimated)
- Results
- Posted 6 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Experimental | Drug: Apixabanapixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (30 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApixabanAlso: Thromboprophylaxisapixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months | Drug | Apixaban |
Primary outcome
Frequency of Symptomatic Venous Thromboembolism
Time frame: 6 months
Symptomatic deep vein thrombosis or pulmonary embolism
Frequency of Major and Clinically Relevant Non-major Bleeding
Time frame: 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.
2 secondary outcomes
Frequency of All-cause Mortality
Time frame: 6 months
Frequency of Atherothrombotic Events
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34582035Kahale LA, Matar CF, Tsolakian I, Hakoum MB, Yosuico VE, Terrenato I, Sperati F, Barba M, Hicks LK, Schunemann H, Akl EA. Antithrombotic therapy for ambulatory patients with multiple myeloma receiving immunomodulatory agents. Cochrane Database Syst Rev. 2021 Sep 28;9(9):CD014739. doi: 10.1002/14651858.CD014739.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Apixaban in people with Venous Thromboembolism and Multiple Myeloma, run by Gregory Piazza at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Symptomatic Venous Thromboembolism (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02958969, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.