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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02369653
• Other study ID #: CV185-155
• Secondary ID: 2014-000328-47
• Status: Completed
• Phase: Phase 3
• Start date: October 22, 2015
• Est. completion date: July 7, 2021

Study information

• Verified date: February 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 512
• Est. completion date: July 7, 2021
• Est. primary completion date: July 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Apixaban

Other:
• No systemic anticoagulant prophylaxis

Locations

Country	Name	City	State
Australia	Monash Medical Centre Clayton	Clayton	Victoria
Australia	Local Institution	New Lambton Heights	New South Wales
Australia	Local Institution	Parkville	Victoria
Australia	Queensland Children's Hospital	Sth Brisbane	Queensland
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Edegem
Belgium	Local Institution	Gent
Belgium	Local Institution	Leuven
Canada	Alberta Children'S Hospital	Calgary	Alberta
Canada	Local Institution	Edmonton	Alberta
Canada	Children'S Hospital London Health Sciences Centre	London	Ontario
Canada	Children'S Hospital Of Eastern Ontario	Ottawa	Ontario
Canada	Local Institution	St, John's	Newfoundland and Labrador
Czechia	Klinika detske onkologie	Brno
Hungary	Local Institution	Budapest
Hungary	Local Institution	Debrecen
Hungary	Local Institution	Pecs
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Monterrey	Nuevo Leon
New Zealand	Local Institution	Christchurch
Poland	Klinika Transplantacji Szpiku Onkologii i Hematologii Dzieciecej	Wroclaw
Poland	Oddzial Hematologii i Onkologii Dzieciecej	Zabrze
Puerto Rico	Local Institution	Caguas
Russian Federation	Local Institution	Kirov
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	St.petersburg
United States	Akron Children'S Hospital	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University Of Michigan Cancer Center	Ann Arbor	Michigan
United States	Childrens Healthcare Of Atlanta - E	Atlanta	Georgia
United States	Dell Children'S Medical Center Of Central Texas	Austin	Texas
United States	Johns Hopkins University	Baltimore	Maryland
United States	Sinai Hospital Of Baltimore	Baltimore	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	St. Luke'S Mountain State Tumor Institute	Boise	Idaho
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Unv. Of Nc At Chapel Hill	Chapel Hill	North Carolina
United States	Cincinnati Children'S Hospital Medical Center	Cincinnati	Ohio
United States	University Hospitals	Cleveland	Ohio
United States	Nationwide Children'S Hospital	Columbus	Ohio
United States	Driscoll Children'S Hospital	Corpus Christi	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Blank Childrens Hospital	Des Moines	Iowa
United States	City of Hope	Duarte	California
United States	Golisano Childrens Hospital of Southwest Florida	Fort Myers	Florida
United States	Shands Hospital At University Of Florida	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Texas Children's Cancer and Hematology Centers	Houston	Texas
United States	Children'S Center For Cancer And Blood Diseases	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University Of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children'S Clinic	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Loma Linda University Cancer Center	Loma Linda	California
United States	Childrens Hospital Of La	Los Angeles	California
United States	University Of Louisville	Louisville	Kentucky
United States	Navicent Health Physician Group	Macon	Georgia
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Childrens Hospitals And Clinics Of Minnesota	Minneapolis	Minnesota
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Children's Hospital at TriStar Centennial	Nashville	Tennessee
United States	Monroe Carell Jr Children'S Hosp. At Vanderbilt Tower	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Childrens Hospital New Orleans	New Orleans	Louisiana
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Children'S Hospital Of Orange County	Orange	California
United States	Nemours Children'S Clinic - Orlando	Orlando	Florida
United States	Lucile Packard Children's Hospital (LPCH)	Palo Alto	California
United States	Valerie Fund Children's Center at St. Joseph's Children's Hospital	Paterson	New Jersey
United States	Nemours Children'S Clinic-Pensacola	Pensacola	Florida
United States	Childrens Hospital Of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children'S Hospital/Ctr. For Cancer & Blood Ctr.	Phoenix	Arizona
United States	Children's Hospital Of Pittsburgh Of UPMC	Pittsburgh	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University Of Rochester General Clinical Research Center	Rochester	New York
United States	All Childrens Hospital Specialty Physicians	Saint Petersburg	Florida
United States	Children's Hospital of San Antonio	San Antonio	Texas
United States	University Hospital	San Antonio	Texas
United States	Rady Children'S Hospital - San Diego	San Diego	California
United States	Providence Sacred Heart Medical Center	Spokane	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	MultiCare Institute for Research & Innovation	Tacoma	Washington
United States	Scott & White - McLane Children's Specialty Clinic	Temple	Texas
United States	New York Medical College	Valhalla	New York
United States	St. Marys Medical Center	West Palm Beach	Florida
United States	Nemours / A. I. duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Hungary,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Puerto Rico,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From first dose up to approximately 40 days after first dose
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: fatal bleeding; clinically overt bleeding associated with a decrease in hemoglobin of at least 20g/L (ie, 2g/dL) in a 24-hour period; bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS; and/or; bleeding that requires surgical intervention in an operating suite, including interventional radiology.	From first dose up to approximately 34 days after first dose
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	From first dose up to approximately 40 days after first dose
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	From first dose up to approximately 34 days after first dose
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	From first dose up to approximately 34 days after first dose
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	From first dose up to approximately 34 days after first dose
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	From first dose up to approximately 34 days after first dose
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: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and; bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room	From first dose up to approximately 34 days after first dose
Secondary	The Number of Participant Deaths	The number of participant deaths adjudicated by a blinded, independent adjudication committee	From first dose date until the end of the treatment period + 30 days (Up to approximately 59 days)
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	From first dose up to approximately 34 days after first dose
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	From first dose up to approximately 34 days after first dose
Secondary	The Number of Participants Needing Catheter Replacements During the Study	The number of participants needing catheter replacements during the study	From first dose up to approximately 34 days after first dose
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	From first dose up to approximately 34 days after first dose
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.	From first dose up to approximately 34 days after first dose
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: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition and; bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room	From first dose up to approximately 34 days after first dose
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	From first dose up to approximately 34 days after first dose
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.	From first dose up to approximately 34 days after first dose
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.	pre-dose, 1-4 hours post dose
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.	pre-dose, 1-4 hours post dose
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.	pre-dose, 1-4 hours post dose
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	pre-dose and 2.5 hours after dosing on day 7. Day 8 and day 15.

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