A Phase III Randomized, Open Label, Multi-center Study of the Safety and Efficacy of Apixaban for Thromboembolism Prevention Versus No Systemic Anticoagulant Prophylaxis During Induction Chemotherapy in Children With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) or Lymphoma (T or B Cell) Treated With Asparaginase
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 512
- Locations
- 73
- Primary Endpoint
- The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death
Study Overview
Brief Summary
The purpose of this study is to compare the effect of a blood thinning drug called Apixaban versus no administration of a blood thinning drug, in preventing blood clots in children with leukemia or lymphoma. Patients must be receiving chemotherapy, including asparaginase, and have a central line (a catheter inserted for administration of medications and blood sampling)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •New diagnosis of de novo ALL, lymphomas (T or B cell), or mixed-phenotype acute leukemia
- •Planned 3-4 drug systemic induction chemotherapy with a corticosteroid, vincristine and a single dose or multiple doses of asparaginase, with or without daunorubicin
- •Functioning Central Venous Access Device
- •Must be able to tolerate oral medication or have it administered via an Nasogastric tube (NGT) or GT tube
- •Males and females,age 1 year(365 days) to < 18 (17 years and 364 days) years.
Exclusion Criteria
- •Subjects scheduled to have > 3 Lumbar Punctures over the course of the study treatment period
- •Prior history of documented DVT or PE in the past 3 months
- •Known inherited bleeding disorder or coagulopathy
- •Major surgery [excluding Central Venous Access Device (CVAD) replacement and bone marrow aspiration and non-open biopsy] within the last 7 days prior to enrollment that may be associated with a risk of bleeding. Open biopsy is considered a major surgery.
- •Uncontrolled severe hypertension at enrollment. Severe hypertension is defined as a systolic or diastolic blood pressure (BP) > 5 mm Hg above the 95th percentile as defined by the National High Blood Pressure Education Program Working Group (NHBPEP) established guidelines for the definition of normal and elevated blood pressure in children
- •Extreme hyperleukocytosis, white blood cell (WBC) counts over 200 x 109/L (200,000/microL) at the time of enrollment
- •Liver dysfunction manifested by SGTP (ALT) > 5X Upper limit of normal (ULN) and/or Aspartate aminotransferase (AST) >5 X ULN and/or direct (conjugated) bilirubin > 2X ULN
- •Renal function < 30% of normal for age and size as determined by the Schwartz formula
- •International normalized ratio (INR) > 1.4 and activated partial thromboplastin time (aPTT) > 3 seconds above the upper limit of normal for age, within 1 week prior to enrollment.
- •History of allergy to apixaban or Factor Xa inhibitors
- •History of significant adverse reaction or major bleeding related adverse reaction to other anticoagulant or antiplatelet agents
- •History of any significant drug allergy (such as anaphylaxis or hepatotoxicity
- •Any investigational drug being administered during the study
- •Other protocol inclusion/exclusion criteria may apply
Arms & Interventions
Apixaban
Children aged 1 to <18 years weighing 6 to <35 kg randomized to apixaban will receive a fixed dose apixaban based on body weight tier twice a day for approximately 28 days.
Children aged 1 to <18 years weighing ≥ 35 kg will receive 2.5 mg of apixaban twice a day for approximately 28 days. Subjects ≥ 5 years may be administered either 2.5-mg, 0.5-mg tablets or oral solution apixaban. Subjects < 5years and < 35 kg may be administered 0.5-mg tablets only
Intervention: Apixaban (Drug)
No systemic anticoagulant prophylaxis
No systemic anticoagulant prophylaxis
Intervention: No systemic anticoagulant prophylaxis (Other)
Outcomes
Primary Outcomes
The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death
Time Frame: From first dose up to approximately 40 days after first dose
The number of participants with non-fatal deep vein thromboses (DVT) (including asymptomatic and symptomatic), pulmonary embolism (PE), cerebral venous sinus thrombosis (CVST); and venous thromboembolism (VTE) related-death objectively confirmed by a blinded, independent adjudication committee. Symptomatic events are included during the intended treatment period. Asymptomatic events are included from scans up to Day 40.
The Number of Participants With Adjudicated Major Bleeding
Time Frame: From first dose up to approximately 34 days after first dose
The number of participants with major bleeding adjudicated by a blinded, independent adjudication committee. Adjudicated major bleeding is defined as bleeding that satisfies one or more of the following criteria: 1. fatal bleeding 2. clinically overt bleeding associated with a decrease in hemoglobin of at least 20g/L (ie, 2g/dL) in a 24-hour period 3. bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS; and/or 4. bleeding that requires surgical intervention in an operating suite, including interventional radiology.
Secondary Outcomes
- The Number of Participants With a CVAD-Related Infection(From first dose up to approximately 34 days after first dose)
- The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)(From first dose up to approximately 40 days after first dose)
- The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)(From first dose up to approximately 34 days after first dose)
- The Number of Participants With Non-fatal Pulmonary Embolism (PE)(From first dose up to approximately 34 days after first dose)
- The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)(From first dose up to approximately 34 days after first dose)
- The Number of Participants With Venous Thromboembolism (VTE)-Related-death(From first dose up to approximately 34 days after first dose)
- The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)(From first dose up to approximately 34 days after first dose)
- The Number of Participant Deaths(From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days))
- The Number of Participants With an Arterial Thromboembolic Event(From first dose up to approximately 34 days after first dose)
- The Number of Participants Needing Catheter Replacements During the Study(From first dose up to approximately 34 days after first dose)
- The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use(From first dose up to approximately 34 days after first dose)
- The Number Participants Experiencing Superficial Vein Thrombosis Events(From first dose up to approximately 34 days after first dose)
- The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)(From first dose up to approximately 34 days after first dose)
- The Number of Participants With Minor Bleeding Events(From first dose up to approximately 34 days after first dose)
- The Number of Platelet Transfusions Needed During the Study(From first dose up to approximately 34 days after first dose)
- Maximum Observed Concentration (Cmax)(pre-dose, 1-4 hours post dose)
- Trough Observed Concentration (Cmin)(pre-dose, 1-4 hours post dose)
- Area Under the Concentration-Time Curve [AUC(TAU)](pre-dose, 1-4 hours post dose)
- Anti-FXa Activity(pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.)