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Leukemia, Lymphoid

Lymphoma

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Neoplasms by Histologic Type

Lymphoproliferative Disorders

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Immunoproliferative Disorders

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Pharmaceutical Solutions

All Drugs and Chemicals

Anticoagulants

Antineoplastic Agents

Anti-Infective Agents

Amino Acids

Apixaban

Asparaginase

Factor Xa Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Enzyme Inhibitors

Serine

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

No systemic anticoagulant prophylaxis

Bristol-Myers Squibb

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)

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

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

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 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.

The number of participants with non-fatal asymptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee

The number of participants with non-fatal symptomatic deep vein thromboses (DVT) adjudicated by a blinded, independent adjudication committee

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) adjudicated by a blinded, independent adjudication committee

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) 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 adjudicated by a blinded, independent adjudication committee

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 central venous access device (CVAD)-related infection adjudicated by a blinded, independent adjudication committee

The number of participants needing catheter replacements during the study

The number of participants with central venous access device (CVAD) patency restoration events after thrombolytic therapy use

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) 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 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.

The events are not adjudicated. A subject could have more than one platelet transfusion.

The maximum observed concentration (Cmax) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.

The trough observed concentration (Cmin) was measured to assess the pharmacokinetics of oral or enteric apixaban in pediatric subjects receiving induction chemotherapy.

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 was measured to characterize the relationship between apixaban plasma concentration and anti-FXa activity in pediatric subjects receiving induction chemotherapy

Pfizer

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

No systemic anticoagulant prophylaxis during induction chemotherapy

Standard of Care

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

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

The Number of Participants With Non-Fatal DVT, PE, and CVST, and VTE-Related-Death

The Number of Participants With Adjudicated Major Bleeding

The Number of Participants With Non-fatal Asymptomatic Deep Vein Thromboses (DVT)

The Number of Participants With Non-fatal Symptomatic Deep Vein Thromboses (DVT)

The Number of Participants With Non-fatal Pulmonary Embolism (PE)

The Number of Participants With Cerebral Venous Sinus Thrombosis (CVST)

The Number of Participants With Venous Thromboembolism (VTE)-Related-death

The Number of Participants With Major and Clinically Relevant Non-Major Bleeding (CRNMB)

The Number of Participant Deaths

The Number of Participants With an Arterial Thromboembolic Event

The Number of Participants With a CVAD-Related Infection

The Number of Participants Needing Catheter Replacements During the Study

The Number of Participants With CVAD Patency Restoration Events After Thrombolytic Therapy Use

The Number Participants Experiencing Superficial Vein Thrombosis Events

The Number of Participants With Clinically Relevant Non-Major Bleeding Events (CRNMB)

The Number of Participants With Minor Bleeding Events

The Number of Platelet Transfusions Needed During the Study

Participants will be administered 2.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase

Participants Weight Range ≥ 35 kg

Participants will be administered 2mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase

Participants Weight Range 25 to < 35 kg

Participants will be administered 1.5mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase

Participants Weight Range 18 to < 25 kg

Participants will be administered 1mg apixaban twice daily by mouth or via a NGT or GT according to weight range during approximately 28 days of induction chemotherapy including asparaginase

Participants Weight Range 10.5 to < 18 kg

All randomized participants in the apixaban arm with available pharmacokinetic data

Maximum Observed Concentration (Cmax)

Trough Observed Concentration (Cmin)

Area Under the Concentration-Time Curve [AUC(TAU)]

Day 7 (Predose)

Day 7 (2.5 hours)

Day 8

Day 15

All randomized participants in the apixaban arm with available pharmacodynamic data

Spots Global Cancer Trial Database for no systemic anticoagulant prophylaxis