Clinical trial NCT04106700: Prophylaxis With Apixaban in Transplant Eligible Patients With Multiple Myeloma Receiving Induction Therapy With IMiDs
Official title: Venous Thromboembolism Prophylaxis With Apixaban in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma Receiving Induction Therapy With an Immunomodulatory-based Regimen
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Venous Thromboembolism
Keywords: Multiple Myeloma
Venous Thromboembolism
Lead sponsor: Instituto de Investigacion Sanitaria La Fe
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2019-09-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Clinical trial with a single arm
Primary purpose: TREATMENT

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).

Eligibility criteria: 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).

Primary outcomes:
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 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)
measure: Venous thromboembolism (VTE)- related death
timeFrame: 14 days after last dose of apixaban
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 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)
measure: Symptomatic deep-vein thrombosis (DVT)
timeFrame: 14 days after last dose of apixaban
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 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)
measure: Pulmonary embolism (PE)
timeFrame: 14 days after last dose of apixaban
measure: Asymptomatic proximal DVT as detected by systematic compression ultrasound
timeFrame: 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)
measure: Asymptomatic proximal DVT as detected by systematic compression ultrasound
timeFrame: 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:
measure: Major bleeding event
timeFrame: 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)
measure: Clinically relevant non-major bleeding event
timeFrame: 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)
measure: Fatal Bleeding Event
timeFrame: 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)
measure: Liver injury event
timeFrame: 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)
measure: Serious adverse events
timeFrame: 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)
measure: Symptomatic DVT or PE occurring during the 90 days of follow-up period
timeFrame: Day +90 follow-up
measure: Death occurring during the 90 days of follow-up period
timeFrame: Day +90 follow-up
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Clinico Universitario
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Valencia
country: Spain
facility: Hospital General Universitario
Study officials:
affiliation: Hospital Doctor Peset
name: Javier de la Rubia
role: STUDY_DIRECTOR
affiliation: Hospital Universitario y Politecnico La Fe
name: Samuel Romero
role: PRINCIPAL_INVESTIGATOR
References: