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A Phase III Randomized Trial for Patients With de Novo AML Using Bortezomib and Sorafenib (IND#114480, NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD


Phase 3
N/A
29 Years
Open (Enrolling)
Both
Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Pure Erythroid Leukemia (M6b), Childhood Acute Erythroleukemia (M6), Childhood Acute Megakaryocytic Leukemia (M7), Childhood Acute Minimally Differentiated Myeloid Leukemia (M0), Childhood Acute Monoblastic Leukemia (M5a), Childhood Acute Monocytic Leukemia (M5b), Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Myeloblastic Leukemia Without Maturation (M1), Childhood Acute Myelomonocytic Leukemia (M4), Untreated Adult Acute Myeloid Leukemia, Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Thank you

Trial Information

A Phase III Randomized Trial for Patients With de Novo AML Using Bortezomib and Sorafenib (IND#114480, NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD


PRIMARY OBJECTIVES:

I. To compare event-free survival (EFS) and overall survival (OS) of patients with de novo
acute myeloid leukemia (AML) with or without high allelic ratio FLT3/ITD+ mutations who are
randomized to standard therapy versus bortezomib/standard combination therapy.

II. To determine the feasibility of combining bortezomib with standard chemotherapy in
patients with de novo AML.

III. To compare the OS and EFS of high-risk patients treated with intensive Induction II
with historical controls from AAML03P1 and COG-AAML0531.

IV. To determine the feasibility of combining sorafenib with standard chemotherapy in
patients with de novo high allelic ratio FLT3/ITD+ AML.

SECONDRY OBJECTIVES:

I. To assess the anti-leukemic activity of sorafenib in patients with de novo high allelic
ratio FLT3/ITD+ AML.

II. To compare the percentage of patients converting from positive MRD to negative MRD after
Intensive Induction II with historical controls from AAML03P1 and AAML0531.

III. To compare OS, disease-free survival (DFS), cumulative incidence of relapse, and
treatment-related mortality from end of Intensification I between patients allocated to best
allogenic donor stem cell transplant (SCT) and comparable patients on COG-AAML0531 who did
not receive allogenic donor SCT.

IV. To compare OS, DFS, cumulative incidence of relapse, treatment-related mortality, and
severe toxicity between patients allocated to matched family donor SCT on AAML103P1 and
AAML0531.

V. To assess the health-related quality of life (HRQOL) of patients treated with
chemotherapy and SCT for AML.

VI. To evaluate bortezomib pharmacokinetics (PK) in patients receiving the combination
regimen.

VII. To obtain sorafenib and metabolite steady state pharmacokinetics and
pharmacokinetic-pharmacodynamic data in subjects with FLT3/ITD receiving sorafenib.

VIII. To compare the changes in shortening fraction/ejection fraction over time between
patients treated with and without dexrazoxane.

IX. To refine the use of minimal-residual disease (MRD) detection with 4-color flow
cytometry.

X. To evaluate the prognostic significance of molecular MRD and its contribution to risk
identification with multidimensional flow cytometry (MDF)-based MRD in patients with
translocations amenable to quantitative RT-PCR (e.g., t(8;21), inv(16), t(9;11), WT1
expression).

XI. To determine the leukemic involvement of the hematopoietic early progenitor cell and its
role in defining response to therapy.

XII. To define the leukemic stem cell population in patients with AML. XIII. To determine
the prevalence and prognostic significance of molecular abnormalities of WT1, RUNX1,
MLL-PTD, TET2, c-CBL, KIT, and other novel AML-associated genes in pediatric AML.

XIV. To correlate the expression of CD74 antigen as well as PSMB5 gene expression and
mutation with response to bortezomib.

XV. To evaluate the changes in protein expression and unfolded protein response (UPR) in
patients with AML. XVI. To determine the expression level of wild-type FLT3, and correlate
with outcome and in vitro sensitivity to FLT3 inhibition.

XVII. To collect biology specimens at diagnosis, treatment time points, and relapse for
future biology studies.

OUTLINE: This is a multicenter, dose-escalation study of sorafenib tosylate and an
open-label randomized study. Patients are stratified according to disease risk (low vs
high). Patients are randomized to 1 of 2 treatment arms or offered treatment on a third arm.

INDUCTION I:

ARM A: Patients receive cytarabine intrathecally (IT) on day 1 and ADE chemotherapy
comprising cytarabine IV over 15-30 minutes on days 1-10; daunorubicin IV over 1-15 minutes
on days 1, 3, and 5; and etoposide IV over 1-2 hours on days 1-5.

ARM B: Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A.
Patients also receive bortezomib IV on days 1, 4, and 8.

ARM C (high-risk [HR] FLT3/ITD+ disease): Patients receive cytarabine IT and ADE
chemotherapy as in Induction I, Arm A and sorafenib tosylate orally (PO) on days 11-28.

INDUCTION II: Patients without HR FLT3/ITD+ disease begin Induction II administration on day
29.

ARM A (low-risk [LR] patients): Patients receive cytarabine IT and ADE chemotherapy as in
Induction I Arm A.

ARM A (HR patients): Patients receive cytarabine IT on day 1 and MA chemotherapy comprising
high-dose cytarabine IV over 1-3 hours on days 1-4, and mitoxantrone IV over 15-30 minutes
on days 3-6.

ARM B (LR patients): Patients receive cytarabine IT, ADE chemotherapy, and bortezomib as in
Induction I Arm B.

ARM B (HR patients): Patients receive cytarabine IT and MA chemotherapy as in Induction II,
Arm A (HR patients) and bortezomib IV on days 1, 4, and 8.

ARM C (patients with HR FLT3/ITD+ disease, cohorts 1 and 2): Patients receive cytarabine IT
on day 1, cytarabine IV over 15-30 minutes on days 1-8, daunorubicin IV over 1-15 minutes on
days 1, 3, and 5, and etoposide IV over 1-2 hours on days 1-5, and sorafenib tosylate PO on
days 1-28.

Patients who achieve complete remission (CR) proceed to Intensification I (beginning on day
29). Patients with refractory disease are off protocol therapy.

INTENSIFICATION I:

ARM A: Patients receive cytarabine IT on day 1 and AE chemotherapy comprising high-dose
cytarabine IV over 1-3 hours, and etoposide IV over 1-2 hours on days 1-5.

ARM B: Patients receive cytarabine IT and AE chemotherapy in Intensification II, Arm A, and
bortezomib IV on days 1, 4, and 8.

ARM C (cohorts 1 and 2): Patients receive cytarabine IT and AE chemotherapy in
Intensification II, Arm A, and sorafenib tosylate PO on daily on days 1-28.

Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT)
beginning on day 29. Patients with refractory disease are off protocol therapy.

INTENSIFICATION II:

ARM A (LR): Patients receive cytarabine IT on day 1 and MA chemotherapy as in Induction II,
Arm A (HR patients).

ARM B (LR): Patients receive cytarabine IT on day 1, MA chemotherapy as in Induction II, Arm
A (HR patients), and bortezomib IV on days 1, 4, and 8.

ARMS A AND B (HR and no donor for SCT): Patients receive high-dose cytarabine IV over 3
hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.

ARM C (HR cohorts 1 and 2): Patients receive cytarabine IT on day 1, MA chemotherapy as in
Induction II, Arm A (HR patients), and sorafenib tosylate PO on days 1-28.

STEM CELL TRANPLANTATION (SCT) (HR patients with matched family [MFD] or unrelated donor):

CONDITIONING REGIMEN: Patients receive fludarabine IV over 30 minutes once daily on days -5
to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.

TRANSPLANTATION: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose
of busulfan.

GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO
beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with
taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and
6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated
donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8
hours on days -3 to -1.

Blood, bone marrow, and tissue samples are collected at baseline and periodically during
study for mutation and translocation analysis, cytogenetic/FISH analysis, gene and protein
expression, and other studies. Some patients (aged 2 to 18 years) and/or parents may
complete questionnaires about health-related quality of life (Pediatric Quality of Life
(PedsQL) 4.0 Generic Core Scale, the PedsQL 3.0 Acute Cancer Module, and the PedsQL
Multidimensional Fatigue Scale) and parental stress (Pediatric Inventory for Parents (PIP)
scale) at baseline and periodically during the study and follow-up.

After completion of study therapy, patients are followed up monthly for 6 months, every 2
months for 6 months, every 3 months for 1 year, every 6 months for 1 year, and then yearly
for up to 8 years.


Inclusion Criteria:



- Patients must be newly diagnosed with de novo acute myelogenous leukemia and must
meet 1 of the following criteria:

- Patients with previously untreated primary AML who meet the customary criteria
for AML with ≥ 20% bone marrow blasts as set out in the 2008 WHO Myeloid
Neoplasm Classification are eligible

- Patients with cytopenias and bone marrow blasts who do not meet the customary
criteria for the diagnosisof AML (patients with < 20% blasts) are eligible if
they have a karyotypic abnormality characteristic ofde novo AML
(t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities),
or ifthey have the unequivocal presence of megakaryoblasts, as set out in the
2008 WHO Myeloid NeoplasmClassification

- Patients with biopsy-proven isolated myeloid sarcoma (myeloblastoma; chloroma,
including leukemiacutis) are eligible

- Patients must meet one of the following criteria:

- Low-risk disease as defined by any of the following:

- Presence of [inv(16)/t(16;16) or t(8;21)] or presence of NPM orCEBPα
mutation, regardless of minimum-residual disease (MRD) status at end of
Induction I

- Standard-risk cytogenetics (neitherfavorable or unfavorable) with negative
MRD (< 0.1%) at end of Induction I

- Patients who do not have MRD data and have non-informative molecular
studies (NPM, CEBPα,and cytogenetics) will be classified as having low-risk
disease

- High-risk disease as defined by any of the following:

- FLT3/ITD+ with high allelic ratio (HR FLT3/ITD+)

- Unfavorablecytogenetics (monosomy 7, monosomy 5, and del5q)

- Standard-risk cytogenetics with positive MRD(≥ 0.1%) at end of Induction I

- Patients with juvenile myelomonocytic leukemia (JMML) are not eligible

- Patients with Philadelphia chromosome positive AML, biphenotypic or bilineal acute
leukemia,or acute promyelocytic leukemia are not eligible

- High-risk patients may have a donor (bone marrow or cord blood) meeting the following
criteria available:

- Matched family donor (MFD)*

- HLA, A, B, C, DRB1, identical, or 1 antigen or allele mismatched

- HLA typing must be performed using molecular high-resolution technique

- All available first-degree family members (parents and siblings) must
be HLA typed

- Use of syngeneic donors will NOT be permitted in this study

- Alternative donor

- HLA, A, B, C, DRB1 identical or 1 antigen- or allele-mismatched unrelated
donor

- HLA A, B, DRB1 4 of 6 antigen-matched unrelated donor cord blood unit with
an adequatecell dose (nucleated cell dose > 3.7x10^7/kg or CD34+ cell dose
> 2 x 10^5/kg)

- Mismatched family member donor with at least one haplotype match, or 5 of 6
antigenphenotypic match

- Patients with any performance status are eligible

- Patients with constitutional trisomy 21 are not eligible

- Patients with any of the following are not eligible:

- Fanconi anemia

- Shwachman syndrome

- Any other known bone marrow failure syndrome

- Another concurrent malignancy

- Not pregnant or nursing

- Negative pregnancy test

- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use aneffective contraceptive method for the duration of their study
participation

- Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any
route), and intrathecal (IT) cytarabinegiven at diagnosis is allowed

- Hydroxyurea and ATRA must be discontinued prior to initiation of protocoltherapy

- No concurrent peripheral blood stem cell transplantation

- Patients who have previously received any other chemotherapy, radiation therapy, or
any otherantileukemic therapy are not eligible for this protocol

- Concomitant administration of strong CYP3A4 inducers and inhibitors (including
clinicallyrelevant moderate inhibitors) is prohibited on both sorafenib cohorts

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Outcome Time Frame:

From the time on study to induction failure, relapse or death, up to 11 years

Safety Issue:

No

Principal Investigator

Richard Aplenc

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02670

NCT ID:

NCT01371981

Start Date:

June 2011

Completion Date:

Related Keywords:

  • Adult Acute Erythroid Leukemia (M6)
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • Adult Pure Erythroid Leukemia (M6b)
  • Childhood Acute Erythroleukemia (M6)
  • Childhood Acute Megakaryocytic Leukemia (M7)
  • Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Childhood Acute Monoblastic Leukemia (M5a)
  • Childhood Acute Monocytic Leukemia (M5b)
  • Childhood Acute Myeloblastic Leukemia With Maturation (M2)
  • Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
  • Childhood Acute Myelomonocytic Leukemia (M4)
  • Untreated Adult Acute Myeloid Leukemia
  • Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
  • Congenital Abnormalities
  • Neoplasms
  • Leukemia
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Monocytic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic

Name

Location

Baylor College of MedicineHouston, Texas  77030
Johns Hopkins UniversityBaltimore, Maryland  21205
Cleveland Clinic FoundationCleveland, Ohio  44195
Roswell Park Cancer InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Rhode Island HospitalProvidence, Rhode Island  02903
Medical City Dallas HospitalDallas, Texas  75230
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Bronson Methodist HospitalKalamazoo, Michigan  49007
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Loyola University Medical CenterMaywood, Illinois  60153
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Loma Linda University Medical CenterLoma Linda, California  92354
Baptist Hospital of MiamiMiami, Florida  33176-2197
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Cedars-Sinai Medical CenterLos Angeles, California  90048
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Eastern Maine Medical CenterBangor, Maine  04401
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Broward General Medical CenterFort Lauderdale, Florida  33316
All Children's HospitalSt. Petersburg, Florida  33701
Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Ochsner Clinic FoundationNew Orleans, Louisiana  70121
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health CenterPortland, Oregon  97227
Driscoll Children's HospitalCorpus Christi, Texas  78466
Scott and White Memorial HospitalTemple, Texas  76508
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Hospital Medical Center of AkronAkron, Ohio  44308
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Overlook HospitalSummit, New Jersey  07902-0220
Winthrop University HospitalMineola, New York  11501
Mount Sinai Medical CenterNew York, New York  10029
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Montefiore Medical CenterBronx, New York  10467-2490
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central TexasAustin, Texas  78723
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Mary Bridge Children's Hospital and Health CenterTacoma, Washington  98415-0299
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Lee Memorial Health SystemFort Myers, Florida  33902
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Children's Hospital of AlabamaBirmingham, Alabama  35233
Connecticut Children's Medical CenterHartford, Connecticut  06106
Vanderbilt UniversityNashville, Tennessee  37232-6305
University of North CarolinaChapel Hill, North Carolina  27599
Duke University Medical CenterDurham, North Carolina  27710
University of RochesterRochester, New York  14642
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Yale UniversityNew Haven, Connecticut  06520
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
University Of VermontBurlington,, Vermont  05403
Albany Medical CenterAlbany, New York  12208
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Oregon Health and Science UniversityPortland, Oregon  97201
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
Virginia Commonwealth UniversityRichmond, Virginia  
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
Seattle Children's HospitalSeattle, Washington  98105
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Childrens Memorial HospitalChicago, Illinois  60614
Kaiser Permanente-OaklandOakland, California  94611
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
University of HawaiiHonolulu, Hawaii  96813
Saint Luke's Mountain States Tumor InstituteBoise, Idaho  83712
Saint Vincent Hospital and Health ServicesIndianapolis, Indiana  46260
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Michigan State University - Breslin Cancer CenterEast Lansing, Michigan  48824-1313
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Saint Barnabas Medical CenterLivingston, New Jersey  07039
New York University Langone Medical CenterNew York, New York  10016
Columbia University Medical CenterNew York, New York  10032
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Mission Hospitals IncAsheville, North Carolina  28801
Saint Vincent HospitalGreen Bay, Wisconsin  54301
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
University of South AlabamaMobile, Alabama  36693
University of IllinoisChicago, Illinois  60612
Cook Children's Medical CenterFort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's HospitalHollywood, Florida  33021
West Virginia University CharlestonCharleston, West Virginia  25304
The Children's Medical Center of DaytonDayton, Ohio  45404
Advocate Lutheran General HospitalPark Ridge, Illinois  60068
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Children's Oncology GroupArcadia, California  91006-3776
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Southern Illinois UniversitySpringfield, Illinois  62702
Riley Hospital for ChildrenIndianapolis, Indiana  46202
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Phoenix Childrens HospitalPhoenix, Arizona  85016
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
Nemours Childrens Clinic - OrlandoOrlando, Florida  32806
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
The Childrens Mercy HospitalKansas City, Missouri  64108
Rainbow Babies and Childrens HospitalCleveland, Ohio  44106
Penn State Hershey Children's HospitalHershey, Pennsylvania  17033
Palmetto Health RichlandColumbia, South Carolina  29203
East Tennessee Childrens HospitalKnoxville, Tennessee  37916
Children's Hospital and Medical Center of OmahaOmaha, Nebraska  68114
Saint Joseph's Regional Medical CenterPaterson, New Jersey  07503
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
Georgia Health Sciences UniversityAugusta, Georgia  30912
Sanford Medical Center-FargoFargo, North Dakota  58122
Children's Hospital ColoradoAurora, Colorado  80045
Floating Hospital for Children at Tufts Medical CenterBoston, Massachusetts  02111
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterDenver, Colorado  80218
Raymond Blank Children's HospitalDes Moines, Iowa  50309
Children's Hospital-Main CampusNew Orleans, Louisiana  70118
The Toledo Hospital/Toledo Children's HospitalToledo, Ohio  43606
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134
T C Thompson Children's HospitalChattanooga, Tennessee  37403
Providence Sacred Heart Medical Center and Children's HospitalSpokane, Washington  99204