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

NCT02958969 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 18-493
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Venous Thromboembolism; Multiple Myeloma

Keywords

venous thromboembolism; multiple myeloma; anticoagulation

Outcome Measures

Primary Outcomes (2)

• Frequency of Symptomatic Venous Thromboembolism

  Symptomatic deep vein thrombosis or pulmonary embolism

  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.

  6 months

Secondary Outcomes (2)

• Frequency of All-cause Mortality

  6 months

• Frequency of Atherothrombotic Events

  6 months

Study Arms (1)

Apixaban

EXPERIMENTAL

apixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months

Drug: Apixaban

Interventions

Apixaban DRUG

apixaban 2.5 mg orally twice daily for primary prevention of VTE for a duration of 6 months

Also known as: Thromboprophylaxis

Apixaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gregory Piazza: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 34582035 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism; Multiple Myeloma

Interventions

apixaban

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study is limited by small sample size. The study included 10 patients receiving IMiD monotherapy for maintenance which are patients at lowest risk for VTE due to the absence of dexamethasone and low disease burden.

Results Point of Contact

• Title: Gregory Piazza
• Organization: BWH

gpiazza@bwh.harvard.edu

6177326984

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: November 5, 2016
• First Posted: November 8, 2016
• Study Start: February 28, 2018
• Primary Completion: June 30, 2019
• Study Completion: November 19, 2019
• Last Updated: December 17, 2019
• Results First Posted: December 6, 2019

Record last verified: 2019-12

Locations

US (2)