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)
Brief Title
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
Categories
Completion Date
Completion Date Type
Actual
Conditions
Lymphoma
Acute Lymphoblastic Leukemia
Eligibility 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
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
Inclusion Criteria
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.
inclusion/
* 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.
inclusion/
Gender
All
Gender Based
false
Keywords
Anticoagulation
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
1 Year
NCT Id
NCT02369653
Org Class
Industry
Org Full Name
Bristol-Myers Squibb
Org Study Id
CV185-155
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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.
Symptomatic events are included during the intended treatment period. Asymptomatic events are included from scans up to Day 40.
Outcome Measure
The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death
Outcome Time Frame
From first dose up to approximately 40 days after first dose
Outcome Description
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.
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.
Outcome Measure
The Number of Participants With Adjudicated Major Bleeding
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Secondary Ids
Secondary Id
2014-000328-47
Secondary Outcomes
Outcome Description
The number of participants with non-fatal asymptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose up to approximately 40 days after first dose
Outcome Measure
The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)
Outcome Description
The number of participants with non-fatal symptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)
Outcome Description
The number of participants with non-fatal pulmonary embolism (PE) adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With Non-fatal Pulmonary Embolism (PE)
Outcome Description
The number of participants with cerebral venous sinus thrombosis (CVST) adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)
Outcome Description
The number of participants with venous thromboembolism (VTE)-related-death adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With Venous Thromboembolism (VTE)-Related-death
Outcome Description
The number of participants with major and clinically relevant non-major bleeding (CRNMB) adjudicated by a blinded, independent adjudication committee
CRNM bleeding is defined as bleeding that satisfies one or both of the following:
1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and
2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
CRNM bleeding is defined as bleeding that satisfies one or both of the following:
1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and
2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)
Outcome Description
The number of participant deaths adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)
Outcome Measure
The Number of Participant Deaths
Outcome Description
The number of participants with an arterial thromboembolic event including paradoxical embolism and stroke adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With an Arterial Thromboembolic Event
Outcome Description
The number of participants with a central venous access device (CVAD)-related infection adjudicated by a blinded, independent adjudication committee
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With a CVAD-Related Infection
Outcome Description
The number of participants needing catheter replacements during the study
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants Needing Catheter Replacements During the Study
Outcome Description
The number of participants with central venous access device (CVAD) patency restoration events after thrombolytic therapy use
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use
Outcome Description
The number participants experiencing superficial vein thrombosis events.
Clots that occur in a superficial vein ie, cephalic vein, basilic vein (upper extremity) or saphenous vein (lower extremity) confirmed by radiographic imaging.
Clots that occur in a superficial vein ie, cephalic vein, basilic vein (upper extremity) or saphenous vein (lower extremity) confirmed by radiographic imaging.
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number Participants Experiencing Superficial Vein Thrombosis Events
Outcome Description
The number of participants with clinically relevant non-major bleeding events (CRNMB) adjudicated by a blinded, independent adjudication committee.
CRNM bleeding is defined as bleeding that satisfies one or both of the following:
1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and
2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
CRNM bleeding is defined as bleeding that satisfies one or both of the following:
1. overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and
2. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)
Outcome Description
The number of participants with minor bleeding events adjudicated by a blinded, independent adjudication committee.
Minor bleeding defined as any overt or macroscopic evidence of bleeding that does not fulfill the criteria for either major bleeding or CRNMB
Minor bleeding defined as any overt or macroscopic evidence of bleeding that does not fulfill the criteria for either major bleeding or CRNMB
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Participants With Minor Bleeding Events
Outcome Description
The number of platelet transfusions needed during the study.
The events are not adjudicated. A subject could have more than one platelet transfusion.
The events are not adjudicated. A subject could have more than one platelet transfusion.
Outcome Time Frame
From first dose up to approximately 34 days after first dose
Outcome Measure
The Number of Platelet Transfusions Needed During the Study
Outcome Description
The maximum observed concentration (Cmax) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Outcome Time Frame
pre-dose, 1-4 hours post dose
Outcome Measure
Maximum Observed Concentration (Cmax)
Outcome Description
The trough observed concentration (Cmin) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Outcome Time Frame
pre-dose, 1-4 hours post dose
Outcome Measure
Trough Observed Concentration (Cmin)
Outcome Description
The area under the concentration-time curve \[AUC(TAU)\] was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Outcome Time Frame
pre-dose, 1-4 hours post dose
Outcome Measure
Area Under the Concentration-Time Curve [AUC(TAU)]
Outcome Description
Anti-FXa Activity was measured to characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy
Outcome Time Frame
pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.
Outcome Measure
Anti-FXa Activity
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
1
Investigators
Investigator Type
Principal Investigator
Investigator Name
Lisa Gennarini
Investigator Email
lfigueir@montefiore.org
Investigator Phone