A Study of the Safety and Effectiveness of Apixaban in Preventing Blood Clots in Children With Leukemia Who Have a Central Venous Catheter and Are Treated With Asparaginase

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Lymphoma; Acute Lymphoblastic Leukemia

Treatments: Other: No systemic anticoagulant prophylaxis; Drug: Apixaban

Study type: Interventional

Funder types: Industry

Identifiers

NCT02369653

CV185-155

2014-000328-47 (EudraCT Number)

Details and patient eligibility

About

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)

Enrollment: 512 patients

Sex: All

Ages: 1 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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512 participants in 2 patient groups, including a placebo group

Apixaban

Experimental group

Description:

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

Treatment:

Drug: Apixaban

No systemic anticoagulant prophylaxis

Placebo Comparator group

Description:

No systemic anticoagulant prophylaxis

Treatment:

Other: No systemic anticoagulant prophylaxis