Venous Thromboembolism Prophylaxis With Apixaban in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma Receiving Induction Therapy With an Immunomodulatory-based Regimen
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Enrollment
- 60
- Locations
- 4
- Primary Endpoint
- Symptomatic deep-vein thrombosis (DVT)
Study Overview
Brief Summary
Interventional, no-randomized, open-label, and single arm multicentre study of apixaban for the prevention of thromboembolic events during induction therapy in transplant-eligible patients with newly diagnosed multiple myeloma who receive bortezomib, thalidomide, and dexamethasone (VTD) during the induction phase of therapy prior to autologous stem cell transplantation (ASCT). The current study is designed to evaluate the efficacy and safety of apixaban during the induction period. Efficacy will be defined as a composite endpoint of acute symptomatic proximal and distal deep venous thrombosis, pulmonary embolism, VTE related deaths, and acute ischemic stroke.
Detailed Description
This study is designed to test the efficacy and safety of the oral anti factor Xa apixaban 2.5 mg given twice daily as a prophylaxis of VTE in transplant-eligible patients with multiple myeloma during the induction therapy with VTD.
Induction therapy prior to ASCT will consist in no less than 4 and no more than 6 cycles of VTD, depending on treatment response. Duration of each cycle is 4 weeks if there is not any disease or treatment-related complication; therefore, treatment duration will be around 4-6 months. Daily Prophylaxis with apixaban will continue up to a maximum of 14 days after the last dose of thalidomide. In addition, there will be an additional observation period of 14 (± 7) days, starting the day after the last dose of study medication (until 28 days after the end of the last cycle of VTD).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed written informed consent
- •Subjects must have documented newly diagnosed symptomatic multiple myeloma requiring front-line treatment.
- •Patients should be considered transplant-eligible
- •Subjects will receive front-line induction therapy with a triplet regimen consisting of bortezomib, thalidomide and dexamethasone (VTD).
- •To enter to the study at the same time of start anti myeloma induction therapy.
- •Ages eligible for study: 18 to 70 years.
- •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
Exclusion Criteria
- •Patients with the diagnosis of plasma cell leukemia, Waldenström macroglobulinemia, POEMS syndrome or amyloidosis of light chain.
- •Patients with smouldering multiple myeloma or monoclonal gammopathy of undeterminated significance.
- •Patients considered non-transplant-eligible.
- •Grade ≥2 of peripheral neuropathy.
- •Prior history of documented any venous thromboembolism and arterial thrombosis event
- •Active or high risk of bleeding.
- •Need for on-going anticoagulant or antiplatelet treatment.
- •Contraindication of anticoagulant prophylaxis
- •Uncontrolled hypertension: systolic blood pressure >200 mmHg and/or diastolic blood pressure >100 mmHg.
- •HIV, HBV or HCV-positive active.
- •Expected survival <6 months.
- •Weight <40 Kg.
- •Low platelet count (<50 x109/L).
- •ALT >3x UNL, bilirubin >2x ULN.
- •Creatinine clearance <30 mL/min.
- •Women of childbearing potential who are unwilling to use an acceptable method of contraception.
- •Women of childbearing potential who are pregnant or breastfeeding.
- •Women with a positive pregnancy test on enrollment, prior to investigational product administration.
- •Administration of any investigational drug currently or within 30 days prior to planned enrollment into this study.
- •Subjects unwilling or unable to comply with study medication instructions or study procedures (e.g. bilateral lower extremity venous ultrasonography).
- •Known allergies to ingredients contained in apixaban.
- •Use of any contraindicated medications with apixaban (see section 5.4.1).
Arms & Interventions
Apixaban (single arm)
Intervention: Apixaban 2.5 MG (Drug)
Outcomes
Primary Outcomes
Symptomatic deep-vein thrombosis (DVT)
Time Frame: 14 days after last dose of apixaban
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Pulmonary embolism (PE)
Time Frame: 14 days after last dose of apixaban
Pleuritic chest pain, dyspnea (shortness of breath), cough, hemoptysis (expectoration of blood or blood-stained sputum), syncope (fainting), lightheadedness/dizziness, tachypnea (rapid breathing), tachycardia (fast heart rate).
Venous thromboembolism (VTE)- related death
Time Frame: 14 days after last dose of apixaban
i.e. death for which VTE can not be excluded as a cause
Asymptomatic proximal DVT as detected by systematic compression ultrasound
Time Frame: Cycle 6 Day 43 (each cycle is 28 days. Treatment will finish on cycle 4 or 6. Treatment with Apixaban will continue until 14 days after cycle 4/6)
Diagnostic assessment of DVT. Presence of any one of the following will be considered diagnostic for the presence of DVT: 1. New or previously undocumented non-compressibility of one or more proximal venous segments (popliteal vein or higher) of the legs on compression ultrasound. 2. Constant intraluminal filing defect(s) in two or more views on contrast venography in one or more venous segments in the legs or pelvis, or involving the inferior vena cava.
Secondary Outcomes
- Fatal Bleeding Event(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 4/ 6 Day 29, Cycle 4/6 Day 43, Day 14 after end of treatment (each cycle is 28 days. Treatment with Apixaban will continue until 14 days after cycle 4 or 6))
- Liver injury event(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 4/ 6 Day 29, Cycle 4/6 Day 43, Day 14 after end of treatment (each cycle is 28 days. Treatment with Apixaban will continue until 14 days after cycle 4 or 6))
- Major bleeding event(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 4/ 6 Day 29, Cycle 4/6 Day 43, Day 14 after end of treatment (each cycle is 28 days. Treatment with Apixaban will continue until 14 days after cycle 4 or 6))
- Clinically relevant non-major bleeding event(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 4/ 6 Day 29, Cycle 4/6 Day 43, Day 14 after end of treatment (each cycle is 28 days. Treatment with Apixaban will continue until 14 days after cycle 4 or 6))
- Serious adverse events(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 4/ 6 Day 29, Cycle 4/6 Day 43, Day 14 after end of treatment (each cycle is 28 days. Treatment with Apixaban will continue until 14 days after cycle 4 or 6))
- Symptomatic DVT or PE occurring during the 90 days of follow-up period(Day +90 follow-up)
- Death occurring during the 90 days of follow-up period(Day +90 follow-up)