Venous ThromboembolismPhase 2NCT04106700
Prophylaxis With Apixaban in Transplant Eligible Patients With Multiple Myeloma Receiving Induction Therapy With IMiDs
A Phase 2 study testing Apixaban 2.5 MG in people with Venous Thromboembolism, run by Instituto de Investigacion Sanitaria La Fe at 4 sites in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Apixaban 2.5 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 4 sitesSpain
- Study dates
- 12 Apr 2019to 5 Oct 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 22Show fewer
- 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).
Trial locations and contacts
4 sites in 1 country.
Spain4 sites
Hospital Clinico Universitario
Valencia, 46010
Hospital Universitario Doctor Peset
Valencia, 46017
Hospital Universitario y Politécnico La Fe
Valencia, 46026
Hospital General Universitario
Valencia
About this study
Official title: Venous Thromboembolism Prophylaxis With Apixaban in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma Receiving Induction Therapy With an Immunomodulatory-based Regimen
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.
Read the 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).
- Conditions
- Venous Thromboembolism
- Being tested
- Apixaban 2.5 MG
- Keywords
- Multiple Myeloma, Venous Thromboembolism
- 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.
Apixaban 2.5 MGDrug
Apixaban will be started simultaneously with anti myeloma treatment on day 1 of cycle 1 of VTD, and continues for 4 to 6 months depending on the number of induction cycles administered to the patient
| Study group | Role | What they receive |
|---|---|---|
| Apixaban (single arm) | Experimental | Not described Receives: Drug: Apixaban 2.5 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 1 Day 1 (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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 2 Day 1 (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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 3 Day 1 (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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 4 Day 1 (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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 5 Day 1(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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 6 Day 1 (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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 4 Day 29 (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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 6 Day 29 (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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: Cycle 4 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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: 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)
Venous thromboembolism (VTE)- related death
i.e. death for which VTE can not be excluded as a cause
Measured: 14 days after last dose of apixaban
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 1 Day 1 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 2 Day 1 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 3 Day 1 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 4 Day 1 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 5 Day 1 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 6 Day 1 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 4 Day 29 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 6 Day 29 (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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: Cycle 4 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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: 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)
Symptomatic deep-vein thrombosis (DVT)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Measured: 14 days after last dose of apixaban
Pulmonary embolism (PE)
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).
Measured: Cycle 1 Day 1 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 2 Day 1 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 3 Day 1 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 4 Day 1 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 5 Day 1 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 6 Day 1 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 4 Day 29 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 6 Day 29 (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)
Pulmonary embolism (PE)
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).
Measured: Cycle 4 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)
Pulmonary embolism (PE)
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).
Measured: 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)
Pulmonary embolism (PE)
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).
Measured: 14 days after last dose of apixaban
Asymptomatic proximal DVT as detected by systematic compression ultrasound
Diagnostic assessment of DVT. Presence of any one of the following will be considered diagnostic for the presence of DVT:
- New or previously undocumented non-compressibility of one or more proximal venous segments (popliteal vein or higher) of the legs on compression ultrasound.
- 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.
Measured: Cycle 4 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)
Asymptomatic proximal DVT as detected by systematic compression ultrasound
Diagnostic assessment of DVT. Presence of any one of the following will be considered diagnostic for the presence of DVT:
- New or previously undocumented non-compressibility of one or more proximal venous segments (popliteal vein or higher) of the legs on compression ultrasound.
- 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.
Measured: 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)
Secondary outcomes (7)
Major bleeding event
Defined as a bleeding event that is acute clinically overt bleeding accompanied by one or more of the following:
- A decrease in hemoglobin (Hb) of 2 g/dL or more over a 24-hour period.
- A transfusion of 2 or more units of packed red blood cells.
- Bleeding that occurs in at least one of the following critical sites: intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, an operated joint and requires re-operation or intervention, intramuscular with compartment syndrome, retroperitoneal.
- Bleeding that is fatal.
Measured: 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
Defined as a bleeding event that is:
- Acute clinically overt bleeding.
- Does not satisfy additional criteria required for the bleeding event to be defined as a major bleeding event and meets at least one of the following criteria:
- Epistaxis: need to medical attention from a physician or visits an emergency room, requires an intervention, persists for 5 minutes or more.
- Gastrointestinal bleed: vomit containing frank blood or coffee ground material which tests positive for blood, endoscopically confirmed bleeding, frank blood per rectum or melena stools.
- Hematuria: overt spontaneous bleeding, bleeding persists for 24 hours or more after instrumentation.
- Bruising/ecchymosis: any bruise, which is assessed as "unusual".
- Hematoma: presence of a hematoma is demonstrated radiographically, and a drop-in hemoglobin is present with no external evidence of bleeding.
- Hemoptysis: expectoration of blood or blood-stained sputum.
Measured: 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)
Fatal Bleeding Event
Defined as a bleeding event that determines is the primary cause of death or contributes directly to death.
Measured: 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
Potential or suspected cases of liver injury including but not limited to liver test abnormalities (elevation of ALT, AST, GGT, alkaline phosphatase and total bilirrubin), jaundice, hepatitis or cholestasis events.
Measured: 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
A Serious Adverse Event is any untoward medical occurrence that:
- Results in death.
- Is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe).
- Requires inpatient hospitalization or prolongation of existing hospitalization
- Results in persistent or significant disability/incapacity.
- Is a congenital anomaly/birth defect.
- Is an important medical event (defined as a medical event(s) that may require medical intervention to prevent one of a serious outcome listed above).
- Overdose.
- Second primary malignancies.
Measured: 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
Symptomatic DTV or PE as defined aforementioned, assessed 90 days after the last dose of the study drug.
Measured: Day +90 follow-up
Death occurring during the 90 days of follow-up period
All cause of mortality occurring during the 90 days after the last dose of the study drug.
Measured: Day +90 follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2019
- Study start12 Apr 2019
- Primary completion26 Aug 2020
- Study completion5 Oct 2020
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Clinical trial with a single arm
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigacion Sanitaria La Fe
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Javier de la Rubia, Study director, Hospital Doctor PesetSamuel Romero, Principal investigator, Hospital Universitario y Politecnico La Fe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04106700
- Sponsor's protocol ID
- APIXABAN
- Status last verified
- Jun 2020
- First submitted
- 20 Sep 2019
- Last updated
- 15 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Venous Thromboembolism Prophylaxis With Apixaban in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma Receiving Induction Therapy With an Immunomodulatory-based Regimen
- ClinicalTrials.gov ID
- NCT04106700
- Acronym / sponsor ID
- APIXABAN
- Conditions
- Venous Thromboembolism
- Keywords
- Multiple Myeloma, Venous Thromboembolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Instituto de Investigacion Sanitaria La FeUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 12 Apr 2019 (actual)
- Primary completion
- 26 Aug 2020 (actual)
- Study completion
- 5 Oct 2020 (actual)
- First posted
- 27 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Clinical trial with a single arm
| Arm | Type | Receives |
|---|---|---|
| Apixaban (single arm) | Experimental | Drug: Apixaban 2.5 MG |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
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 |
|---|---|---|
| Apixaban 2.5 MGApixaban will be started simultaneously with anti myeloma treatment on day 1 of cycle 1 of VTD, and continues for 4 to 6 months depending on the number of induction cycles administered to the patient | Drug | Apixaban (single arm) |
Primary outcome
Venous thromboembolism (VTE)- related death
Time frame: Cycle 1 Day 1 (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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 2 Day 1 (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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 3 Day 1 (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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 4 Day 1 (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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 5 Day 1(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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 6 Day 1 (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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 4 Day 29 (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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 6 Day 29 (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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
Time frame: Cycle 4 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)
i.e. death for which VTE can not be excluded as a cause
Venous thromboembolism (VTE)- related death
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)
i.e. death for which VTE can not be excluded as a cause
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
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 1 Day 1 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 2 Day 1 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 3 Day 1 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 4 Day 1 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 5 Day 1 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 6 Day 1 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 4 Day 29 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 6 Day 29 (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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
Time frame: Cycle 4 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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
Symptomatic deep-vein thrombosis (DVT)
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)
Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness
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: Cycle 1 Day 1 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 2 Day 1 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 3 Day 1 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 4 Day 1 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 5 Day 1 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 6 Day 1 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 4 Day 29 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 6 Day 29 (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)
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).
Pulmonary embolism (PE)
Time frame: Cycle 4 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)
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).
Pulmonary embolism (PE)
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)
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).
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).
Asymptomatic proximal DVT as detected by systematic compression ultrasound
Time frame: Cycle 4 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.
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.
7 secondary outcomes
Major bleeding event
Time frame: 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
Time frame: 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)
Fatal Bleeding Event
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day +90 follow-up
Death occurring during the 90 days of follow-up period
Time frame: Day +90 follow-up
Results and safety
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2021.
- Individual participant dataSharing planned: No
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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.
Javier de la Rubia study director
Hospital Doctor Peset
Samuel Romero principal investigator
Hospital Universitario y Politecnico La Fe
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apixaban 2.5 MG in people with Venous Thromboembolism, run by Instituto de Investigacion Sanitaria La Fe at 4 sites in Spain.
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 22 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: stopped early, as of the sponsor's last update on 15 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
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?
Venous thromboembolism (VTE)- related death (time frame: Cycle 1 Day 1 (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)). The study lists 35 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Feb 2021.