Clinical trial NCT00557193: Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Official title: A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Lymphoblastic Leukemia
Acute Undifferentiated Leukemia
Childhood T Acute Lymphoblastic Leukemia
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-11-12
Enrollment: 218
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia.

Detailed description: PRIMARY OBJECTIVES:

I. To estimate the 3-year event-free survival (EFS) of infants with mixed lineage leukemia-rearranged (MLL-R) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus the fms-related tyrosine kinase 3 (FLT3) inhibitor lestaurtinib.

SECONDARY OBJECTIVES:

I. To compare the 3-year EFS of infants with MLL-R ALL treated with chemotherapy plus the FLT3 inhibitor lestaurtinib to MLL-R patients treated with chemotherapy alone.

II. To determine a safe, tolerable and biologically active dose of lestaurtinib given in sequential combination with chemotherapy in MLL-R infants.

III. To characterize the pharmacokinetics and pharmacodynamics of lestaurtinib in infants when given at the proposed dose in sequential combination with chemotherapy.

IV. To identify molecular mechanisms of resistance to lestaurtinib in leukemic blasts.

V. To describe levels of minimal residual disease in infants with ALL within the context of the proposed therapy, and correlate with outcome.

VI. To identify gene expression patterns in diagnostic infant leukemia samples that correlate with outcome within the context of the proposed therapy.

VII. To describe the outcome of infants with MLL-G ALL treated with a modified P9407 chemotherapy backbone that includes an extended continuation phase.

OUTLINE:

INDUCTION THERAPY (WEEKS 1-5): All patients receive induction therapy comprising vincristine sulfate intravenously (IV) over 1 minute on days 8, 15, 22, and 29; daunorubicin hydrochloride IV over 30 minutes on days 8 and 9; cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 (closed as of 05/19/09); pegaspargase or asparaginase intramuscularly (IM) on days 15, 18, 22, 25, 29, and 33; prednisone orally (PO) thrice daily (TID) or methylprednisolone IV on days 1-7; dexamethasone IV or PO TID on days 8-28; cytarabine IV over 30 minutes on days 8-21; methotrexate intrathecally (IT) on days 1 and 29; cytarabine IT on day 15; hydrocortisone IT on days 15 and 29; and filgrastim IV or subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Standard-risk patients are non-randomly assigned to receive a less intensive chemotherapy regimen without lestaurtinib (post-induction therapy A). Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), blood sample collection and bone marrow biopsy on day 1 week 1.

POST-INDUCTION THERAPY A: (for standard-risk patients MLL-germline \[G\])

INDUCTION INTENSIFICATION (WEEKS 6-9): Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on days 1 and 8; leucovorin calcium IV or PO every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is \< 0.1 uM; cyclophosphamide IV over 30 minutes on days 15-19; etoposide IV over 2 hours on days 15-19; and filgrastim IV or SC beginning on day 20 and continuing until blood counts recover. Patients in morphologic remission proceed to re-induction therapy. Patients may undergo bone marrow biopsy on day 1 week 6.

RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; daunorubicin hydrochloride IV over 30 minutes on days 1 and 2; cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4; pegaspargase or asparaginase IM on day 4; dexamethasone IV or PO twice daily (BID) on days 1-7 and 15-21; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on days 1 and 15; and filgrastim IV or SC beginning on day 5 and continuing until blood counts recover. Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 10.

CONSOLIDATION (WEEKS 13-19): Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8; leucovorin calcium IV every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is \< 0.1 uM; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on day 1; etoposide IV over 2 hours on days 15-19; cyclophosphamide IV over 30 minutes on days 15-19; high-dose cytarabine IV over 3 hours every 12 hours on days 29 and 30; pegaspargase or asparaginase IM on day 30; and filgrastim IV or SC beginning on day 20 and day 31 and continuing until blood counts recover.

CONTINUATION I (WEEKS 20-41): Patients receive vincristine sulfate IV on day 1 in weeks 20 and 24; dexamethasone IV or PO BID on days 1-5 in weeks 20, and 24; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on day 1 in weeks 20 and 24; methotrexate IV on day 1 in weeks 21-24 and 25-27; etoposide IV over 2 hours on day 1-5 in week 28; cyclophosphamide IV over 30 minutes on days 1-5 in week 28; mercaptopurine PO on days 1-7 in weeks 21-23 and 25-27; and filgrastim SC or IV beginning on day 6 in week 28 and continuing until blood counts recover. Patients may undergo bone marrow biopsy on day 1 week 20.

CONTINUATION II (WEEKS 42-104): Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone IV or PO BID on days 1-5, 29-33, and 57-61; methotrexate IT on day 1; methotrexate PO on days 8, 15, 22, 36, 43, 50, 64, 71, and 78; and mercaptopurine PO on days 8-28, 36-56, and 64-84. Treatment repeats every 12 weeks for 2 years from diagnosis.

A safety/activity phase is conducted separately for the intermediate-risk (IR) and high-risk (HR) patients to identify a safe, tolerable, and biologically active dose of lestaurtinib combined with chemotherapy backbone. Once a tolerable/active dose of lestaurtinib has been identified for IR patients, subsequent IR patients are eligible to proceed to an efficacy phase, where they are randomized (or non-randomly assigned as of 7/16/2014) to chemotherapy with or without lestaurtinib. HR patients separately proceed to the randomized efficacy phase if a tolerable/active dose is identified for the HR stratum. IR and HR patients are randomized (or non-randomly assigned as of 7/16/2014) to 1 of 2 post-induction therapy regimens (post-induction therapy B or C).

POST-INDUCTION THERAPY B: (chemotherapy only for IR/HR patients classified as MLL-R; age \>= 90 days at diagnosis):

INDUCTION INTENSIFICATION (WEEKS 6-9): Patients receive high-dose methotrexate, leucovorin calcium, cyclophosphamide, etoposide, and filgrastim as in post-induction therapy A induction intensification. Patients in morphologic remission proceed to re-induction Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 6. (Retired as of 7/16/2014)

RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, pegaspargase or asparaginase, dexamethasone, triple IT chemotherapy, and filgrastim as in post-induction therapy A re-induction. Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 10. (Retired as of 7/16/2014)

CONSOLIDATION (WEEKS 13-19): Patients receive high-dose methotrexate, leucovorin calcium, triple IT chemotherapy, etoposide, cyclophosphamide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy A consolidation. (Retired as of 7/16/2014)

CONTINUATION I (WEEKS 20-49): Patients receive vincristine sulfate IV over 1 minute on day 1 in weeks 20, 24, 33, 37, and 46; dexamethasone PO or IV BID on days 1-5 in weeks 20, 24, 33, 37, and 46; triple IT chemotherapy on day 1 in weeks 20, 24, 33, 37, and 46; methotrexate IV on day 1 in weeks 21-23, 25-26 and 37-45; mercaptopurine PO on days 1-7 in weeks 21-23, 25-26 and 37-45; etoposide IV over 2 hours on days 1-5 in week 27; cyclophosphamide IV over 2 hours on days 1-5 in week 27: high-dose cytarabine IV over 3 hours every 12 hours on days 1 and 2 in week 30; pegaspargase or asparaginase IM on day 2 in week 30: and filgrastim SC or IV beginning on day 3 in weeks 30 and continuing until blood counts recover. Patients may undergo bone marrow biopsy on day 1 of weeks 20, 33 and 46. (Retired as of 7/16/2014)

CONTINUATION II (WEEKS 50-104): Patients receive vincristine sulfate, dexamethasone, IT methotrexate, methotrexate PO, and mercaptopurine PO as in post-induction therapy A continuation II. Treatment repeats every 12 weeks for 2 years from diagnosis. (Retired as of 7/16/2014)

POST-INDUCTION THERAPY C: (chemotherapy and lestaurtinib for IR/HR patients classified as MLL-R; age \< 90 days at diagnosis)

INDUCTION INTENSIFICATION THERAPY (WEEKS 6-9): Patients receive high-dose methotrexate, leucovorin calcium, cyclophosphamide, etoposide, and filgrastim as in post-induction therapy B induction intensification. Patients also receive lestaurtinib PO BID on days 20-27. Patients in morphologic remission proceed to re-induction.Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 6.

RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, pegaspargase or asparaginase, dexamethasone, triple IT chemotherapy, and filgrastim as in post-induction therapy B re-induction. Patients also receive lestaurtinib PO on days 5-20. Patients undergo ECHO or MUGA, blood sample collection and bone marrow biopsy on day 1 week 10.

CONSOLIDATION (WEEKS 13-19) Patients receive high-dose methotrexate, leucovorin calcium, triple IT chemotherapy, etoposide, cyclophosphamide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy B consolidation. Patients also receive lestaurtinib PO on days 20-27 and 31-42.

CONTINUATION I (WEEKS 20-49): Patients receive vincristine sulfate, dexamethasone, triple IT chemotherapy, methotrexate, mercaptopurine, etoposide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy B continuation I. Patients also receive lestaurtinib PO on days 2-6 in weeks 20 and 24; days 27-41 in weeks 27-29; days 45-56 in weeks 30-32. Patients may undergo bone marrow biopsy on day 1 of weeks 20, 33 and 46.

CONTINUATION II (WEEKS 50-104): Patients receive vincristine sulfate, dexamethasone, IT methotrexate, methotrexate PO, and mercaptopurine PO as in post-induction therapy B continuation II. Treatment repeats every 12 weeks for 2 years from diagnosis.

After completion of study treatment, all patients are followed up every 1-6 months for 4 years and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Patients must be enrolled on a Children's Oncology Group (COG) ALL Classification Study (AALL08B1) prior to enrollment on AALL0631
* Patients must be \< 366 days of age at the time of diagnosis; for neonates in the first month of life, patients must be \> 36 weeks gestational age at the time of diagnosis
* Patients must be newly diagnosed with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL); patients with T-cell ALL are eligible; patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominately lymphoid
* Patients must be previously untreated with the exception of steroids and intrathecal chemotherapy; no other systemic chemotherapy may have been administered; patients receiving prior steroid therapy are eligible for study; any amount of steroid pretreatment will not affect initial induction assignment as long as the patient meets all other eligibility criteria; IT chemotherapy per protocol is allowed for patient convenience at the time of the diagnostic bone marrow or venous line placement to avoid second lumbar puncture; (note: the central nervous system \[CNS\] status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
* Patients with mature B-cell ALL or acute myelogenous leukemia (AML) are NOT eligible
* Patients with Down syndrome are NOT eligible

Primary outcomes:
measure: Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2)
timeFrame: From start of post-induction therapy for up to 10 years
Secondary outcomes:
measure: Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2
timeFrame: From start of post-induction therapy for up to 10 years.
measure: Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT)
timeFrame: Up to 12 weeks from start of induction
measure: Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy
timeFrame: Up to 12 weeks
measure: Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy
timeFrame: Up to 12 weeks
measure: Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy
timeFrame: Sampled between weeks 6-12 from start of induction
measure: Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts
timeFrame: Sampled at the start of induction
measure: Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts
timeFrame: At relapse (up to 3 years)
measure: Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts
timeFrame: Sampled at the start of induction
measure: Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts
timeFrame: At relapse (up to 3 years)
measure: Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm
timeFrame: 3 Years from end of Induction)
measure: Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With Survival Outcomes
timeFrame: At 3 years
measure: Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With PIA Values
timeFrame: At 3 years
measure: Percent Probability for Event-free Survival (EFS) for Patients on Arm A
timeFrame: From start of post-induction therapy for up to 10 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Kaiser Permanente Downey Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Long Beach
country: United States
facility: Miller Children's and Women's Hospital Long Beach
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Parnassus
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mission Bay
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Lee Memorial Health System
state: Florida
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Science Center - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic - Orlando
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hospital/Children's Hospital-Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Honolulu
country: United States
facility: Tripler Army Medical Center
state: Hawaii
city: Boise
country: United States
facility: Saint Luke's Cancer Institute - Boise
state: Idaho
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Children's Hospital-Oak Lawn
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Children's Hospital-Park Ridge
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: Ascension Saint Vincent Indianapolis Hospital
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital New Orleans
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University Clinical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Kalamazoo Center for Medical Studies
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: Columbia Regional
state: Missouri
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center of Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: Alliance for Childhood Diseases/Cure 4 the Kids Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Summerlin Hospital Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation NCORP
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: Mercy Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Columbia
country: United States
facility: Prisma Health Richland Hospital
state: South Carolina
city: Greenville
country: United States
facility: BI-LO Charities Children's Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Cancer Treatment Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center-Amarillo
state: Texas
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Burlington
country: United States
facility: University of Vermont and State Agricultural College
state: Vermont
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: Mary Bridge Children's Hospital and Health Center
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Charleston
country: United States
facility: West Virginia University Charleston Division
state: West Virginia
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center Green Bay
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Medical Center-Marshfield
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John's
country: Canada
facility: Janeway Child Health Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: London
country: Canada
facility: Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: The Montreal Children's Hospital of the MUHC
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Grafton
country: New Zealand
facility: Starship Children's Hospital
state: Auckland
Study officials:
affiliation: Children's Oncology Group
name: Joanne M Hilden
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loftus JP, Yahiaoui A, Brown PA, Niswander LM, Bagashev A, Wang M, Schauf A, Tannheimer S, Tasian SK. Combinatorial efficacy of entospletinib and chemotherapy in patient-derived xenograft models of infant acute lymphoblastic leukemia. Haematologica. 2021 Apr 1;106(4):1067-1078. doi: 10.3324/haematol.2019.241729.