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Standard Risk B-precursor Acute Lymphoblastic Leukemia


Phase 3
1 Year
9 Years
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

Standard Risk B-precursor Acute Lymphoblastic Leukemia


OBJECTIVES:

Primary

- Compare event-free survival of pediatric patients with newly diagnosed, standard-risk
(SR)-average, B-precursor acute lymphoblastic leukemia (ALL) treated with induction
therapy followed by 1 of 4 intensified phases of post-induction therapy.

- Compare event-free survival of pediatric patients with SR-low ALL treated with
consolidation and interim maintenance therapy with or without additional pegaspargase.

Secondary

- Correlate day 29 minimal residual disease (MRD) status with event-free survival and
overall survival of patients treated with these regimens.

- Correlate early marrow response with day 29 MRD status in patients treated with these
regimens.

- Determine whether outcome is improved for SR-high patients by identifying these
patients by day 29 MRD status and subsequently treating these patients with a fully
augmented Berlin Frankfurt Munster regimen.

- Correlate relative contributions of genetic factors and early treatment response with
outcome in patients treated with these regimens.

OUTLINE: This is a 2-part, partially randomized, multicenter study. Patients are stratified
according to early response to study induction therapy (rapid early response [standard risk
(SR)-low or SR-average acute lymphoblastic leukemia (ALL)] vs slow early response [SR-high
ALL]). After completion of induction therapy but before proceeding to part II therapy,
patients are assigned to 1 of 3 groups based on stratification.

Part I

- Induction therapy: All patients receive cytarabine intrathecally (IT) on day 1;
vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally twice daily on days
1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or
6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3
disease). Patients with Down syndrome (DS) receive oral leucovorin calcium at 48 and 60
hours after each dose of methotrexate IT .

Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal
residual disease (MRD) < 0.1% OR MRD ≥ 0.1% and < 1% proceed to therapy in part II. Patients
with M2 bone marrow OR M1 bone marrow AND MRD ≥ 1% proceed to extended induction therapy.
Patients with M3 bone marrow are removed from the study.

- Extended induction therapy: Patients receive dexamethasone IV or orally twice daily on
days 1-14; vincristine IV on days 1 and 8; pegaspargase IM on day 4, 5, or 6; and
daunorubicin hydrochloride IV over 15 minutes to 2 hours on day 1.

Patients with M1 bone marrow and MRD < 1% after extended induction therapy proceed to
therapy in part II. Patients with M2 or M3 bone marrow after extended induction therapy are
removed from the study.

Part II

- Group 1 (SR-low ALL): Patients are randomized to 1 of 2 treatment arms.

- Arm I:

- Standard consolidation therapy: Patients receive vincristine IV on day 1;
oral mercaptopurine on days 1-28; and methotrexate IT on days 1, 8, and 15.
Patients with Down syndrome (DS) receive oral leucovorin calcium at 48 and 60
hours after each dose of methotrexate IT.

- Standard interim maintenance therapy: Patients receive vincristine IV on days
1 and 29; dexamethasone IV or orally twice daily on days 1-5 and 29-33; oral
mercaptopurine on days 1-50; oral methotrexate on days 1, 8, 15, 22, 29, 36,
43, and 50; and methotrexate IT on day 29. Patients with DS receive oral
leucovorin calcium at 48 and 60 hours after each dose of methotrexate IT.

- Standard delayed intensification (DI) therapy: Patients receive vincristine
IV on days 1, 8, and 15; dexamethasone IV or orally twice daily on days 1-21;
doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15;
pegaspargase IM on day 4, 5, or 6; cyclophosphamide IV over 30 minutes on day
29; cytarabine IV or subcutaneously (SC) on days 29-32 and 36-39; oral
thioguanine on days 29-42; and methotrexate IT on days 1 and 29. Patients
with DS receive dexamethasone IV or orally twice daily on days 1-7 and 15-21
and oral leucovorin calcium at 48 and 60 hours after each dose of
methotrexate IT.

- Arm II:

- Experimental consolidation therapy: Patients receive vincristine,
mercaptopurine, methotrexate, and leucovorin calcium as in arm I and
pegaspargase IM on days 1 and 22.

- Experimental interim maintenance therapy: Patients receive vincristine,
dexamethasone, mercaptopurine, oral methotrexate, and methotrexate IT as in
arm I and pegaspargase IM on days 15 and 36.

- Standard DI therapy: Patients receive standard DI therapy as in arm I.

- Group 2 (SR-average ALL): Patients are randomized to 1 of 4 treatment arms.

- Arm I: Patients receive standard consolidation therapy, standard interim
maintenance therapy, and standard DI therapy as in group 1, arm I.

- Arm II:

- Standard consolidation therapy: Patients receive standard consolidation
therapy as in group 1, arm I.

- Augmented interim maintenance therapy: Patients receive vincristine IV and
methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and
22; and methotrexate IT on days 1 and 31. Patients with DS receive oral
leucovorin calcium at 48 and 60 hours after each dose of methotrexate IT.

- Augmented DI therapy: Patients receive vincristine IV on days 1, 8, 15, 43,
and 50; dexamethasone IV or orally twice daily on days 1-21; doxorubicin
hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15;
pegaspargase IM on day 4, 5, or 6 AND day 43; cyclophosphamide IV over 30
minutes on day 29; cytarabine IV or SC on days 29-32 and 36-39; oral
thioguanine on days 29-42; and methotrexate IT on days 1, 29, and 36.
Patients with DS receive dexamethasone on days 1-7 and 15-21 and oral
leucovorin calcium at 48 and 60 hours after each dose of methotrexate IT.

- Arm III:

- Intensified consolidation therapy: Patients receive cyclophosphamide IV over
30 minutes on days 1 and 29; cytarabine IV or SC on days 1-4, 8-11, 29-32,
and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days
15, 22, 43, and 50; pegaspargase IM on days 15 and 43; and methotrexate IT on
days 1, 8, 15*, and 22*. Patients with DS receive oral leucovorin calcium at
48 and 60 hours after each dose of methotrexate IT*.

NOTE: *Patients with CNS3 disease at diagnosis do not receive methotrexate on days 15 and 22
or leucovorin calcium

- Standard interim maintenance therapy: Patients receive standard interim maintenance
therapy as in group 1, arm I.

- Standard DI therapy: Patients receive standard DI therapy as in group 1, arm I.

- Arm IV:

- Intensified consolidation therapy: Patients receive intensified consolidation therapy
as in group 2, arm III.

- Augmented interim maintenance therapy: Patients receive augmented interim maintenance
therapy as in group 2, arm II.

- Augmented DI therapy: Patients receive augmented DI therapy as in group 2, arm II.

- Group 3 (SR-high ALL): Patients receive the following therapy:

- Intensified consolidation therapy: Patients receive intensified consolidation
therapy as in group 2, arm III.

- Augmented interim maintenance* therapy: Patients receive augmented interim
maintenance therapy as in group 2, arm II. Treatment repeats every 56 days
for 2 courses.

NOTE: *As of Amendment #7, all SR-High patients currently receiving AIM 1 therapy should
complete this phase of therapy and proceed to ADI 1 therapy as originally planned including
Capizzi methotrexate during AIM 1. Upon completion of ADI 1, patients should receive a
second Interim Maintenance phase with high-dose methotrexate (IM HD) rather than Capizzi
methotrexate. Patients should then proceed to ADI 2 and then Maintenance.

- Augmented DI* therapy: Patients receive augmented DI therapy as in group 2, arm II.
Treatment repeats every 56 days for 2 courses**.

NOTE: *As of Amendment #7, all SR-High patients currently receiving ADI 1 therapy should
complete this phase of therapy as originally planned. Upon completion of ADI 1, patients
should receive a second Interim Maintenance phase with IM HD. Patients should then proceed
to ADI 2 and then Maintenance.

NOTE: **Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy on days
29-33 and 36-40 during course 2 only; these patients do not receive methotrexate on day 36,
thioguanine, or leucovorin calcium.

- Maintenance therapy: All patients receive vincristine IV on days 1, 29, and 57; oral
dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral methotrexate on days 8,
15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and
methotrexate IT* on day 1. Courses repeat every 84 days for a total of 2 years from the
start of interim maintenance therapy for female patients and 3 years from the start of
interim maintenance therapy for male patients.

NOTE: *SR-High or CNS3 patients should receive up to a maximum of 23 intrathecal treatments
for females and 26 intrathecal treatments for males.

After the completion of study treatment, patients are followed every 1-2 months for 2 years,
every 3 months for 1 year, and then every 6-12 months for 2 years.

PROJECTED ACCRUAL: A total of 3,381 patients (1,576 for group 1,278 for group 2, and 527 for
group 3) will be accrued for this study within 4.25 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed B-precursor acute lymphoblastic leukemia

- Standard-risk (SR) disease meeting 1 of the following criteria:

- SR-average by age and WBC

- No unfavorable features

- Rapid early responder (RER) by day 15

- CNS 1 or 2

- Minimal residual disease (MRD) negative on day 29

- Trisomies of 4, 10, and 17 or TEL-AML1 translocation and RER and CNS2
allowed

- SR-low by age and WBC

- No unfavorable features

- RER by day 15

- MRD negative on day 29

- CNS1

- Favorable cytogenetics-trisomies of 4, 10, and 17 or TEL-AML
translocation

- SR-high

- Unfavorable features meeting ≥ 1 of the following criteria:

- MLL rearrangements and RER

- Steroid pretreatment

- CNS3

- Slow early responder by morphology or MRD

- Patients with Down syndrome are allowed

- Concurrently enrolled on COG-AALL03B1

PATIENT CHARACTERISTICS:

Age

- 1 to under 10

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- Initial WBC < 50,000/mm^3

Hepatic

- Not specified

Renal

- Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior cytotoxic chemotherapy except intrathecal cytarabine

Endocrine therapy

- Prior steroid therapy allowed at the discretion of the investigator

- No contraindication to additional asparaginase therapy after induction for the
standard risk-low study

Radiotherapy

- No concurrent intensity-modulated radiotherapy

Surgery

- Not specified

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 (EFS) for SR-average

Outcome Description:

All power calculations are based on the assumption of proportional hazards, and using the log rank test (alpha = 0.05) with four planned analyses of the data for interim monitoring purposes. The 95% confidence interval for EFS for standard risk-high will also be computed

Outcome Time Frame:

Up to 6 years

Safety Issue:

No

Principal Investigator

Kelly Maloney, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Colorado Center for Cancer and Blood Disorders

Authority:

United States: Federal Government

Study ID:

AALL0331

NCT ID:

NCT00103285

Start Date:

January 2005

Completion Date:

Related Keywords:

  • Leukemia
  • untreated childhood acute lymphoblastic leukemia
  • B-cell childhood acute lymphoblastic leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
Walter Reed Army Medical CenterWashington, District of Columbia  20307-5000
University of Chicago Cancer Research CenterChicago, Illinois  60637
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
Hurley Medical CenterFlint, Michigan  48503
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
CCOP - KalamazooKalamazoo, Michigan  49007-3731
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health CenterFarmington, Connecticut  06360-2875
Baystate Regional Cancer Program at D'Amour Center for Cancer CareSpringfield, Massachusetts  01199
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
CCOP - MeritCare HospitalFargo, North Dakota  58122
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792-6164
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
UMASS Memorial Cancer Center - University CampusWorcester, Massachusetts  01605-2982
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Sutter Cancer CenterSacramento, California  95816
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Schneider Children's HospitalNew Hyde Park, New York  11042
St. Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134-1095
Driscoll Children's HospitalCorpus Christi, Texas  78466
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
East Tennessee Children's HospitalKnoxville, Tennessee  37901
Covenant Children's HospitalLubbock, Texas  79410
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Midwest Children's Cancer Center at Children's Hospital of WisconsinMilwaukee, Wisconsin  53226
Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Overlook HospitalSummit, New Jersey  07902-0220
Winthrop University HospitalMineola, New York  11501
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Kaiser Permanente Medical Center - OaklandSacramento, California  95825
Santa Barbara Cottage Children's HospitalSanta Barbara, California  93105
Yale Cancer CenterNew Haven, Connecticut  06520-8028
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Broward General Medical Center Cancer CenterFt. Lauderdale, Florida  33316
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
Baptist-South Miami Regional Cancer ProgramMiami, Florida  33176
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Blank Children's HospitalDes Moines, Iowa  50309
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Floating Hospital for Children at Tufts - New England Medical CenterBoston, Massachusetts  02111
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Mount Sinai Medical CenterNew York, New York  10029
Stony Brook University Cancer CenterStony Brook, New York  11794-8174
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
Rhode Island Hospital Comprehensive Cancer CenterProvidence, Rhode Island  02903
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Texas Tech University Health Sciences Center School of Medicine - AmarilloAmarillo, Texas  79106
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Naval Medical Center - PortsmouthPortsmouth, Virginia  23708-2197
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
William Beaumont Hospital - Royal Oak CampusRoyal Oak, Michigan  48073
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
University of South Alabama Mitchell Cancer InstituteMobile, Alabama  36604
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos Angeles, California  90048-1865
Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781
Childrens Hospital Los AngelesLos Angeles, California  90027
Children's Hospital and Research Center OaklandOakland, California  94609
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Children's Hospital Center for Cancer and Blood DisordersAurora, Colorado  80045
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
University of Illinois Cancer CenterChicago, Illinois  60612-7243
Keyser Family Cancer Center at Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Advocate Lutheran General Cancer Care CenterPark Ridge, Illinois  60068-1174
Simmons Cooper Cancer InstituteSpringfield, Illinois  62794-9677
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
Maine Children's Cancer Program at Barbara Bush Children's HospitalScarborough, Maine  04074-9308
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Masonic Cancer Center at University of MinnesotaMinneapolis, Minnesota  55455
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Children's HospitalOmaha, Nebraska  68114-4113
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Albany Medical Center HospitalAlbany, New York  12208-3419
Akron Children's HospitalAkron, Ohio  44308-1062
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Dayton Children's - DaytonDayton, Ohio  45404-1815
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
Legacy Emanuel Hospital and Health Center and Children's HospitalPortland, Oregon  97227
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central TexasAustin, Texas  78723
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Carilion Medical Center for Children at Roanoke Community HospitalRoanoke, Virginia  24014
Madigan Army Medical Center - TacomaTacoma, Washington  98431
Mary Bridge Children's Hospital and Health Center - TacomaTacoma, Washington  98405
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
University of Virginia Cancer CenterCharlottesville, Virginia  22908
Massachusetts General HospitalBoston, Massachusetts  02114-2617
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
Stanford Cancer CenterStanford, California  94305-5824
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
Leo W. Jenkins Cancer Center at ECU Medical SchoolGreenville, North Carolina  27834
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Penn State Hershey Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Greenville Hospital Cancer CenterGreenville, South Carolina  29605
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403
Banner Desert Medical CenterMesa, Arizona  85202