Prophylaxis With Apixaban in Transplant Eligible Patients With Multiple Myeloma Receiving Induction Therapy With IMiDs

NCT04106700 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: APIXABAN
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

Venous Thromboembolism

Keywords

Multiple Myeloma; Venous Thromboembolism

Outcome Measures

Primary Outcomes (35)

• Venous thromboembolism (VTE)- related death

  i.e. death for which VTE can not be excluded as a cause

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  14 days after last dose of apixaban

• Symptomatic deep-vein thrombosis (DVT)

  Lower extremity DVT: erythema (redness of the skin), warmth, pain, swelling, tenderness

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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: 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.

  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: 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.

  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

  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)

• 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)

• 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)

Study Arms (1)

Apixaban (single arm)

EXPERIMENTAL

Drug: Apixaban 2.5 MG

Interventions

Apixaban 2.5 MG DRUG

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

Apixaban (single arm)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Investigacion Sanitaria La Fe: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Hospital Clinico Universitario

Valencia, 46010, Spain

Location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Hospital General Universitario

Valencia, Spain

Location

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

Study Officials

• Javier de la Rubia

  Hospital Doctor Peset

  STUDY DIRECTOR

• Samuel Romero

  Hospital Universitario y Politecnico La Fe

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Clinical trial with a single arm

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 27, 2019
• Study Start: April 12, 2019
• Primary Completion: August 26, 2020
• Study Completion: October 5, 2020
• Last Updated: February 15, 2021

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)