Acute Lymphoblastic Leukemia, Lymphoma
Conditions
Keywords
Anticoagulation
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)
Interventions
DRUGApixaban
OTHERNo systemic anticoagulant prophylaxis
Sponsors
Pfizer
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 non-fatal pulmonary embolism (PE) adjudicated by a blinded, independent adjudication committee |
| 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 cerebral venous sinus thrombosis (CVST) adjudicated by a blinded, independent adjudication committee |
| 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 venous thromboembolism (VTE)-related-death adjudicated by a blinded, independent adjudication committee |
| 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 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 |
| 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 participant deaths adjudicated by a blinded, independent adjudication committee |
| The Number of Participants With an Arterial Thromboembolic Event | From first dose up to approximately 34 days after first dose | The number of participants with an arterial thromboembolic event including paradoxical embolism and stroke adjudicated by a blinded, independent adjudication committee |
| 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 a central venous access device (CVAD)-related infection adjudicated by a blinded, independent adjudication committee |
| 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 needing catheter replacements during the study |
| 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 asymptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee |
| The Number Participants Experiencing Superficial Vein Thrombosis Events | From first dose up to approximately 34 days after first dose | 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. |
| 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 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 |
| The Number of Participants With Minor Bleeding Events | From first dose up to approximately 34 days after first dose | 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 |
| The Number of Platelet Transfusions Needed During the Study | From first dose up to approximately 34 days after first dose | The number of platelet transfusions needed during the study. The events are not adjudicated. A subject could have more than one platelet transfusion. |
| Maximum Observed Concentration (Cmax) | pre-dose, 1-4 hours post dose | The maximum observed concentration (Cmax) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy. |
| Trough Observed Concentration (Cmin) | pre-dose, 1-4 hours post dose | The trough observed concentration (Cmin) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy. |
| Area Under the Concentration-Time Curve [AUC(TAU)] | pre-dose, 1-4 hours post dose | 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. |
| Anti-FXa Activity | pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15. | Anti-FXa Activity was measured to characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy |
| 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 of participants with central venous access device (CVAD) patency restoration events after thrombolytic therapy use |
| 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 symptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee |
Countries
Australia, Belgium, Canada, Czechia, Hungary, Mexico, New Zealand, Poland, Puerto Rico, Russia, South Korea, United States
Participant flow
Pre-assignment details
512 participants were randomized. 256 is the number of subjects who randomized to each of Apixaban or Standard of Care arm respectively.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban Participants will be administered apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase.
Weight range - Dose
\>/=35 kg - 2.5 mg twice daily \<35 to 25 kg - 2 mg twice daily \<25 to 18 kg - 1.5 mg twice daily \<18 to 10.5 kg - 1 mg twice daily \<10.5 to 6 kg - 0.5 mg twice daily | 256 |
| Standard of Care No systemic anticoagulant prophylaxis during induction chemotherapy | 256 |
| Total | 512 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 0 | 1 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Participant withdrew consent | 13 | 3 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Apixaban |
|---|---|---|---|
| Age, Continuous | 7.1 Years STANDARD_DEVIATION 4.39 | 7.2 Years STANDARD_DEVIATION 4.36 | 7.2 Years STANDARD_DEVIATION 4.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 63 Participants | 122 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 192 Participants | 388 Participants | 196 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 27 Participants | 52 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 24 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 22 Participants | 45 Participants | 23 Participants |
| Race (NIH/OMB) White | 194 Participants | 388 Participants | 194 Participants |
| Sex: Female, Male Female | 107 Participants | 222 Participants | 115 Participants |
| Sex: Female, Male Male | 149 Participants | 290 Participants | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 250 | 4 / 262 |
| other Total, other adverse events | 204 / 250 | 193 / 262 |
| serious Total, serious adverse events | 91 / 250 | 83 / 262 |
Outcome results
Primary
The Number of Participants With Adjudicated Major Bleeding
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.
Time frame: From first dose up to approximately 34 days after first dose
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Adjudicated Major Bleeding | 2 Participants |
| Standard of Care | The Number of Participants With Adjudicated Major Bleeding | 2 Participants |
p-value: 1Cochran-Mantel-Haenszel
Primary
The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death
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.
Time frame: From first dose up to approximately 40 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death | 31 Participants |
| Standard of Care | The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death | 45 Participants |
p-value: 0.0403Cochran-Mantel-Haenszel
Secondary
Anti-FXa Activity
Anti-FXa Activity was measured to characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy
Time frame: pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.
Population: All randomized participants in the apixaban arm with available pharmacodynamic data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apixaban | Anti-FXa Activity | Day 15 | 70.2 Anti-FXa activity (ng/mL) | Standard Deviation 28 |
| Apixaban | Anti-FXa Activity | Day 7 (Predose) | 55.3 Anti-FXa activity (ng/mL) | Standard Deviation 16.4 |
| Apixaban | Anti-FXa Activity | Day 7 (2.5 hours) | 78.7 Anti-FXa activity (ng/mL) | Standard Deviation 28.8 |
| Apixaban | Anti-FXa Activity | Day 8 | 55.2 Anti-FXa activity (ng/mL) | Standard Deviation 8.96 |
| Standard of Care | Anti-FXa Activity | Day 15 | 75.3 Anti-FXa activity (ng/mL) | Standard Deviation 33.9 |
| Standard of Care | Anti-FXa Activity | Day 7 (2.5 hours) | 72.1 Anti-FXa activity (ng/mL) | Standard Deviation 30.6 |
| Standard of Care | Anti-FXa Activity | Day 7 (Predose) | 62.2 Anti-FXa activity (ng/mL) | Standard Deviation 19.4 |
| Participants Weight Range 18 to < 25 kg | Anti-FXa Activity | Day 7 (Predose) | 52.8 Anti-FXa activity (ng/mL) | Standard Deviation 16 |
| Participants Weight Range 18 to < 25 kg | Anti-FXa Activity | Day 7 (2.5 hours) | 77.5 Anti-FXa activity (ng/mL) | Standard Deviation 30.8 |
| Participants Weight Range 18 to < 25 kg | Anti-FXa Activity | Day 8 | 47.5 Anti-FXa activity (ng/mL) | Standard Deviation 10.6 |
| Participants Weight Range 18 to < 25 kg | Anti-FXa Activity | Day 15 | 63.9 Anti-FXa activity (ng/mL) | Standard Deviation 21.6 |
| Participants Weight Range 10.5 to < 18 kg | Anti-FXa Activity | Day 15 | 64.8 Anti-FXa activity (ng/mL) | Standard Deviation 25.3 |
| Participants Weight Range 10.5 to < 18 kg | Anti-FXa Activity | Day 7 (Predose) | 44.2 Anti-FXa activity (ng/mL) | Standard Deviation 12.9 |
| Participants Weight Range 10.5 to < 18 kg | Anti-FXa Activity | Day 7 (2.5 hours) | 87.5 Anti-FXa activity (ng/mL) | Standard Deviation 45.5 |
| Participants Weight Range 10.5 to < 18 kg | Anti-FXa Activity | Day 8 | 48 Anti-FXa activity (ng/mL) | Standard Deviation 11.3 |
Secondary
Area Under the Concentration-Time Curve [AUC(TAU)]
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.
Time frame: pre-dose, 1-4 hours post dose
Population: All randomized participants in the apixaban arm with available pharmacokinetic data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Apixaban | Area Under the Concentration-Time Curve [AUC(TAU)] | 470 ng•h/mL | Geometric Coefficient of Variation 35.3 |
| Standard of Care | Area Under the Concentration-Time Curve [AUC(TAU)] | 510 ng•h/mL | Geometric Coefficient of Variation 42.7 |
| Participants Weight Range 18 to < 25 kg | Area Under the Concentration-Time Curve [AUC(TAU)] | 453 ng•h/mL | Geometric Coefficient of Variation 44.8 |
| Participants Weight Range 10.5 to < 18 kg | Area Under the Concentration-Time Curve [AUC(TAU)] | 416 ng•h/mL | Geometric Coefficient of Variation 48.5 |
Secondary
Maximum Observed Concentration (Cmax)
The maximum observed concentration (Cmax) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Time frame: pre-dose, 1-4 hours post dose
Population: All randomized participants in the apixaban arm with available pharmacokinetic data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Apixaban | Maximum Observed Concentration (Cmax) | 56.5 ng/mL | Geometric Coefficient of Variation 36.5 |
| Standard of Care | Maximum Observed Concentration (Cmax) | 63.6 ng/mL | Geometric Coefficient of Variation 38.6 |
| Participants Weight Range 18 to < 25 kg | Maximum Observed Concentration (Cmax) | 61.4 ng/mL | Geometric Coefficient of Variation 43.9 |
| Participants Weight Range 10.5 to < 18 kg | Maximum Observed Concentration (Cmax) | 54.2 ng/mL | Geometric Coefficient of Variation 46.8 |
Secondary
The Number of Participant Deaths
The number of participant deaths adjudicated by a blinded, independent adjudication committee
Time frame: From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participant Deaths | 1 Participants |
| Standard of Care | The Number of Participant Deaths | 3 Participants |
Secondary
The Number of Participants Needing Catheter Replacements During the Study
The number of participants needing catheter replacements during the study
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants Needing Catheter Replacements During the Study | 3 Participants |
| Standard of Care | The Number of Participants Needing Catheter Replacements During the Study | 2 Participants |
Secondary
The Number of Participants With a CVAD-Related Infection
The number of participants with a central venous access device (CVAD)-related infection adjudicated by a blinded, independent adjudication committee
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With a CVAD-Related Infection | 1 Participants |
| Standard of Care | The Number of Participants With a CVAD-Related Infection | 6 Participants |
Secondary
The Number of Participants With an Arterial Thromboembolic Event
The number of participants with an arterial thromboembolic event including paradoxical embolism and stroke adjudicated by a blinded, independent adjudication committee
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With an Arterial Thromboembolic Event | 0 Participants |
| Standard of Care | The Number of Participants With an Arterial Thromboembolic Event | 0 Participants |
Secondary
The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)
The number of participants with cerebral venous sinus thrombosis (CVST) adjudicated by a blinded, independent adjudication committee
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST) | 0 Participants |
| Standard of Care | The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST) | 1 Participants |
Secondary
The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)
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
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB) | 11 Participants |
| Standard of Care | The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB) | 3 Participants |
Secondary
The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use
The number of participants with central venous access device (CVAD) patency restoration events after thrombolytic therapy use
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use | 0 Participants |
| Standard of Care | The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use | 0 Participants |
Secondary
The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)
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
Time frame: From first dose up to approximately 34 days after first dose
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB) | 13 Participants |
| Standard of Care | The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB) | 5 Participants |
Secondary
The Number of Participants With Minor Bleeding Events
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
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Minor Bleeding Events | 37 Participants |
| Standard of Care | The Number of Participants With Minor Bleeding Events | 20 Participants |
Secondary
The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)
The number of participants with non-fatal asymptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
Time frame: From first dose up to approximately 40 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT) | 27 Participants |
| Standard of Care | The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT) | 38 Participants |
Secondary
The Number of Participants With Non-fatal Pulmonary Embolism (PE)
The number of participants with non-fatal pulmonary embolism (PE) adjudicated by a blinded, independent adjudication committee
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Non-fatal Pulmonary Embolism (PE) | 0 Participants |
| Standard of Care | The Number of Participants With Non-fatal Pulmonary Embolism (PE) | 0 Participants |
Secondary
The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)
The number of participants with non-fatal symptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT) | 4 Participants |
| Standard of Care | The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT) | 6 Participants |
Secondary
The Number of Participants With Venous Thromboembolism (VTE)-Related-death
The number of participants with venous thromboembolism (VTE)-related-death adjudicated by a blinded, independent adjudication committee
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number of Participants With Venous Thromboembolism (VTE)-Related-death | 0 Participants |
| Standard of Care | The Number of Participants With Venous Thromboembolism (VTE)-Related-death | 0 Participants |
Secondary
The Number of Platelet Transfusions Needed During the Study
The number of platelet transfusions needed during the study. The events are not adjudicated. A subject could have more than one platelet transfusion.
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban | The Number of Platelet Transfusions Needed During the Study | 266 Platelet Transfusions |
| Standard of Care | The Number of Platelet Transfusions Needed During the Study | 248 Platelet Transfusions |
Secondary
The Number Participants Experiencing Superficial Vein Thrombosis Events
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.
Time frame: From first dose up to approximately 34 days after first dose
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Apixaban | The Number Participants Experiencing Superficial Vein Thrombosis Events | 4 Participants |
| Standard of Care | The Number Participants Experiencing Superficial Vein Thrombosis Events | 2 Participants |
Secondary
Trough Observed Concentration (Cmin)
The trough observed concentration (Cmin) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.
Time frame: pre-dose, 1-4 hours post dose
Population: All randomized participants in the apixaban arm with available pharmacokinetic data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Apixaban | Trough Observed Concentration (Cmin) | 18.8 ng/mL | Geometric Coefficient of Variation 57.8 |
| Standard of Care | Trough Observed Concentration (Cmin) | 18.1 ng/mL | Geometric Coefficient of Variation 97.4 |
| Participants Weight Range 18 to < 25 kg | Trough Observed Concentration (Cmin) | 12 ng/mL | Geometric Coefficient of Variation 142 |
| Participants Weight Range 10.5 to < 18 kg | Trough Observed Concentration (Cmin) | 12.9 ng/mL | Geometric Coefficient of Variation 113 |