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Intensified Methotrexate, Nelarabine (Compound 506U78; IND #52611) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) or T-cell Lymphoblastic Lymphoma


Phase 3
1 Year
30 Years
Open (Enrolling)
Both
Contiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Stage II Adult T-cell Leukemia/Lymphoma, Stage II Childhood Lymphoblastic Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Childhood Lymphoblastic Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Childhood Lymphoblastic Lymphoma, T-cell Adult Acute Lymphoblastic Leukemia, T-cell Childhood Acute Lymphoblastic Leukemia, Untreated Adult Acute Lymphoblastic Leukemia, Untreated Childhood Acute Lymphoblastic Leukemia

Thank you

Trial Information

Intensified Methotrexate, Nelarabine (Compound 506U78; IND #52611) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) or T-cell Lymphoblastic Lymphoma


PRIMARY OBJECTIVES:

I. Compare the relative safety and efficacy of augmented Berlin-Frankfurt-Münster-86
multiagent chemotherapy with or without nelarabine in younger patients with newly diagnosed
T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-NHL).

II. Compare the relative safety and efficacy of interim maintenance therapy comprising
high-dose methotrexate (with leucovorin calcium rescue) and mercaptopurine vs
escalating-dose methotrexate (without leucovorin calcium rescue) and pegaspargase in these
patients.

III. Gain preliminary data on the use of nelarabine in patients with high-risk T-NHL and its
effect on long-term survival.

SECONDARY OBJECTIVES:

I. Determine the relative safety and efficacy of withholding radiotherapy in patients with
low -risk T-ALL and administering prophylactic cranial radiotherapy in patients with
intermediate- or high-risk T-ALL.

II. Characterize T-NHL biologic samples using conventional immunophenotyping, cytogenetic
analysis, detection of activating Notch 1 mutations, comparative genomic hybridization
(CGH), and gene expression profiling, and correlate these with long-term survival and
identify potential targets for future therapy.

OUTLINE: This is a randomized, controlled, factorial-group, multicenter study.

INDUCTION THERAPY: (weeks 1-5) Patients receive cytarabine intrathecally (IT) on day 1;
vincristine IV and daunorubicin hydrochloride IV on days 1, 8, 15, and 22; prednisone IV or
orally twice daily on days 1-28; pegaspargase intramuscularly (IM) or IV over 1-2 hours on
day 4, 5, OR 6; and methotrexate (MTX) IT on days 8 and 29*. Patients with Down syndrome
(DS) also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose (DS
patients excluded as of 09/29/10).

After completion of induction therapy, patients undergo risk assessment. Patients with M1
marrow and minimal residual disease (MRD) < 1% (defined as low- and intermediate-risk)
proceed to consolidation therapy at day 36 or when blood counts recover (whichever occurs
later). Patients with M2 marrow (5-25% blasts) and/or MRD ≥ 1% (defined as high-risk)
proceed to consolidation therapy as soon as possible (i.e., they should not wait until day
36 or for blood counts to recover). Patients with M3 marrow (≥ 25% blasts) (defined as
induction failure) proceed to consolidation therapy as soon as possible.

NOTE: *Patients with CNS3 disease also receive MTX IT on days 15 and 22.

CONSOLIDATION THERAPY: (weeks 6-13) During the safety phase portion of the study, patients
with low-risk or intermediate-risk disease are randomized to arms I or III. Patients with
high-risk disease are randomized to arms I, II, III, or IV. (safety phase closed for accrual
as of 09/29/10) During the efficacy phase portion of the study, patients with low-risk*
disease are randomized to arms I and III. Patients with intermediate-risk or high-risk**
disease are randomized to arms I, II, III, or IV. The safety phase ends when the first 20
high-risk patients to receive nelarabine have been evaluated. Patients with DS are
nonrandomly assigned to arm I (DS patients excluded as of 09/29/10). Patients with
induction failure*** are nonrandomly assigned to arm IV.

NOTE: *Patients with T-cell lymphoblastic lymphoma (T-NHL) are nonrandomly assigned to arm
I.

NOTE: ** Patients with T-NHL are randomly assigned to arms I or II without cranial
radiotherapy.

NOTE: *** Patients with T-NHL are nonrandomly assigned to arm II.

ARM I: Patients receive MTX IT on days 1, 8, 15, and 22*; cyclophosphamide IV over 30
minutes on days 1 and 29; cytarabine IV or subcutaneously (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;
and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with persistent
testicular disease or with DS and testicular disease undergo testicular radiotherapy on days
11-12, 15-19, and 22-26 (DS patients excluded as of 09/29/10). Patients with
intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic cranial
radiotherapy (CRT) (1,200 cGy/dose) once daily on days 15-21 and 22-28. Patients with
low-risk disease do not undergo CRT.

NOTE: *Patients with CNS3 disease omit MTX IT on days 15 and 22; patients with high-risk
disease omit MTX IT on day 1 and add an extra dose at day 29.

ARM II: Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; MTX IT on days
15, 22*, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV or
SC on days 8-11, 15-18, 50-53 and 57-60; oral mercaptopurine on days 8-21 and 50-63;
vincristine IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days
22 and 64. Patients with persistent testicular disease or with DS and testicular disease
undergo testicular radiotherapy on days 15, 22-26, and 29-33(DS patients excluded as of
09/29/10). Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo
prophylactic CRT once daily on days 22-28 and 29-35.

NOTE: *Patients with CNS3 disease omit MTX IT on day 22.

ARM III: Patients receive MTX, cyclophosphamide, cytarabine, mercaptopurine, vincristine,
and pegaspargase as in arm I. Patients with persistent testicular disease or with DS and
testicular disease undergo testicular radiotherapy as in arm I (DS patients excluded as of
09/29/10).

ARM IV: Patients receive nelarabine, MTX, cyclophosphamide, cytarabine, mercaptopurine,
vincristine, and pegaspargase as in arm II. Patients with persistent testicular disease or
with DS and testicular disease undergo testicular radiotherapy as in arm II (DS patients
excluded as of 09/29/10). Once blood counts recover, patients proceed to interim maintenance
therapy according to their randomized/assigned arm. Patients not achieving M1 marrow by the
end of consolidation therapy are removed from the study.

INTERIM MAINTENANCE THERAPY (weeks 14-21 for arms I and III; weeks 17-24 for arms II and
IV):

ARM I: Patients* receive vincristine IV and escalating doses of MTX IV on days 1, 11, 21,
31, and 41; pegaspargase** IM or IV over 1-2 hours on days 2 and 22; and MTX IT on days 1
and 31. Patients with DS also receive oral leucovorin calcium 48 and 60 hours after each MTX
IT dose (DS patients excluded as of 09/29/10).

NOTE: * Patients with T-NHL are randomized or assigned to arms I or II only.

NOTE: **Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4,
6, 8, 10, 12, 22, 24, 26, 28, 30, and 32.

ARM II: Patients* receive vincristine, escalating doses of MTX, pegaspargase, and MTX IT as
in arm I.

ARM III: Patients receive high-dose methotrexate (HDMTX) IV over 24 hours and vincristine IV
on days 1, 15, 29, and 43; oral mercaptopurine on days 1-56; and MTX IT on days 1 and 29.
Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or
orally once every 6 hours for 3 doses.

ARM IV: Patients receive HDMTX, vincristine, mercaptopurine, MTX IT, and leucovorin calcium
as in arm III.

Once blood counts recover, patients proceed to delayed intensification therapy according to
their randomized/assigned arm.

DELAYED INTENSIFICATION THERAPY (weeks 22-30 for arms I and III; weeks 25-33 for arms II and
IV):

ARM I: Patients* receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or
orally twice daily on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21
(for patients ≥ 10 years of age and for patients with DS); doxorubicin hydrochloride IV over
15 minutes on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND
day 43; MTX IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29;
cytarabine IV or SC on days 29-32 and 36-39; and oral thioguanine on days 29-42. Patients
with DS also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose (DS
patients excluded as of 09/29/10).

NOTE: *T-NHL patients with standard-risk are nonrandomly assigned to arm I.

ARM II: Patients** receive vincristine IV on days 1, 8, 15, and 50; dexamethasone IV or
orally twice daily on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21
(for patients ≥ 10 years of age); doxorubicin hydrochloride IV over 15 minutes on days 1, 8,
and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; MTX IT on days 1,
36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes
on day 36; cytarabine IV or SC on days 36-39 and 43-46; and oral thioguanine on days 36-49.

NOTE: ** T-NHL patients with induction failure are nonrandomly assigned to arm II.

ARM III: Patients receive vincristine, dexamethasone, doxorubicin hydrochloride,
pegaspargase, MTX IT, cyclophosphamide, cytarabine, and thioguanine as in arm I. Patients
with intermediate- or high-risk disease (CNS1 or CNS2 disease) undergo prophylactic CRT
(1,200 cGy/dose) once daily on days 50-54 and 57-59.

ARM IV: Patients receive vincristine, dexamethasone, doxorubicin hydrochloride,
pegaspargase, MTX IT, nelarabine, cyclophosphamide, cytarabine, and thioguanine as in arm
II. Patients with intermediate- or high-risk disease (CNS 1 or CNS2 disease) undergo
prophylactic CRT on days 50-54 and 57-59.

All patients with CNS3 disease at diagnosis undergo CRT (1,800cGy/dose) once daily on days
50-54 and 57-61. Once blood counts recover, patients proceed to maintenance therapy
according to their randomized/assigned arm.

MAINTENANCE THERAPY (week 31 until the end of therapy for arms I and III; weeks 34-69 for
arms II and IV):

ARM I: Patients* receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice
daily on days 1-5, 29-33, and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX**
on days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, and 78; and MTX IT on day 1. Treatment
repeats every 84 days until the total duration of study treatment is 2 years from the start
of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and 3 years
from the start of interim maintenance therapy (approximately week 171) (for boys with
T-ALL).

NOTE: * Patients with T-NHL and standard-risk are nonrandomly assigned to arm I.

NOTE: **Patients with low-risk disease receive MTX IT, instead of oral MTX, on day 29 during
the first 4 courses of therapy.

ARM II: Patients*** receive vincristine IV on days 1 and 57; oral dexamethasone on days 1-5
and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX on days 8, 15, 22, 29, 36,
43, 50, 57, 64, 71, and 78; MTX IT on day 1; and nelarabine IV over 60 minutes on days
29-33. Treatment (that includes nelarabine) repeats every 84 days for 3 courses. Patients
then receive treatment (without nelarabine) as follows: vincristine IV on days 1 and 57;
oral dexamethasone on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral MTX
on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and MTX IT on day 1. Treatment
(without nelarabine) repeats every 84 days until the total duration of study treatment is 2
years from the start of interim maintenance therapy (approximately week 121) (for girls with
T-ALL) and 3 years from the start of interim maintenance therapy (approximately week 173)
(for boys with T-ALL).

NOTE: *** T-NHL patients with induction failure are nonrandomly assigned to arm II.

ARM III: Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX*, and MTX IT
as in arm I. Treatment repeats every 84 days until the total duration of study treatment is
2 years from the start of interim maintenance therapy (approximately week 119) (for girls
with T-ALL) and 3 years from the start of interim maintenance therapy (approximately week
171) (for boys with T-ALL).

NOTE: *Patients with low-risk disease receive MTX IT, instead of oral MTX, on day 29 during
the first 4 courses of therapy.

ARM IV: Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX, MTX IT, and
nelarabine as in arm II. Patients then receive treatment (without nelarabine) as follows:
vincristine, dexamethasone, mercaptopurine, oral MTX, and MTX IT as in arm II. Treatment
(without nelarabine) repeats every 84 days until the total duration of study treatment is 2
years from the start of interim maintenance therapy (approximately week 121) (for girls with
T-ALL) and 3 years from the start of interim maintenance therapy (approximately week 173)
(for boys with T-ALL).

After completion of study therapy, patients are followed periodically for at least 10 years.


Inclusion Criteria:



- Newly diagnosed with 1 of the following:

- T-cell acute lymphoblastic leukemia (ALL), meeting the following criteria:

- Leukemic blasts lack myeloperoxidase or evidence of B-lineage
derivation(CD19/CD22/CD20) AND express either surface or cytoplasmic CD3 or
two or more of the antigens CD8,CD7, CD5, CD4, CD2 or CD1a

- If surface CD3 is expressed on all leukemic cells, additional markers of
immaturity, including TdT, CD34, or CD99 will be assessed for expression

- Concurrently enrolled on protocol COG-AALL03B1 and/or COG-AALL08B1

- T-lineage lymphoblastic lymphoma (T-NHL)

- Stage II-IV disease

- No B-lineage lymphoblastic lymphoma

- No morphologically unclassifiable lymphoma

- No absence of both B-cell and T-cell phenotype markers

- No CNS3-positive or testicular involvement

- No patients with ALL or T-NHL and Down syndrome

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No peripheral neurotoxicity ≥ grade 2 (for patients randomized to receive nelarabine)

- No prior seizure disorder (for patients randomized to receive nelarabine)

- Prior steroid therapy allowed

- No prior cytotoxic chemotherapy except intrathecal cytarabine

- At least 2 years since prior and no concurrent anticonvulsant therapy (for patients
randomized to receive nelarabine)

- No concurrent milk or citrus products during thioguanine or mercaptopurine
administration

- No concurrent intensity-modulated radiotherapy

- No concurrent nonsteroidal anti-inflammatory drugs, penicillin, or acetylsalicylic
acid-containing medications for at least 3 days after high-dose methotrexate

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Event-free survival (EFS) after initial remission

Outcome Description:

This outcome can be modeled reasonably well by a linear decreasing hazard rate with no appreciable risk of failure after completion of year 4. EFS events include any type of relapse, death in remission or second malignant neoplasm. "Intent-to-treat" analyses (i.e. based on the regimen to which patients are initially randomized) will be the primary approach used to assess treatment efficacy.

Outcome Time Frame:

At 4 years

Safety Issue:

No

Principal Investigator

Stuart Winter

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00307

NCT ID:

NCT00408005

Start Date:

January 2007

Completion Date:

Related Keywords:

  • Contiguous Stage II Adult Lymphoblastic Lymphoma
  • Noncontiguous Stage II Adult Lymphoblastic Lymphoma
  • Stage II Adult T-cell Leukemia/Lymphoma
  • Stage II Childhood Lymphoblastic Lymphoma
  • Stage III Adult Lymphoblastic Lymphoma
  • Stage III Adult T-cell Leukemia/Lymphoma
  • Stage III Childhood Lymphoblastic Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Adult T-cell Leukemia/Lymphoma
  • Stage IV Childhood Lymphoblastic Lymphoma
  • T-cell Adult Acute Lymphoblastic Leukemia
  • T-cell Childhood Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

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
Mayo ClinicRochester, Minnesota  55905
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
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
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
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Marshfield ClinicMarshfield, Wisconsin  54449
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
Madigan Army Medical CenterTacoma, Washington  98431-5048
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
Children's National Medical CenterWashington, District of Columbia  20010-2970
Broward General Medical CenterFort Lauderdale, Florida  33316
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Ochsner Clinic FoundationNew Orleans, Louisiana  70121
Maine Children's Cancer ProgramScarborough, Maine  04074-9308
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
Weill Medical College of Cornell UniversityNew York, New York  10021
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Brooklyn Hospital CenterBrooklyn, New York  11201
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Covenant Children's HospitalLubbock, Texas  79410
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
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
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
City of Hope Medical CenterDuarte, California  91010
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Lee Memorial Health SystemFort Myers, Florida  33902
University of VirginiaCharlottesville, Virginia  22908
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 FloridaGainesville, Florida  32610-0277
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
Wayne State UniversityDetroit, Michigan  48202
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
University of Arizona Health Sciences CenterTucson, Arizona  85724
University of Massachusetts Medical SchoolWorcester, Massachusetts  01605
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
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
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
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
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
Kalamazoo Center for Medical StudiesKalamazoo, Michigan  49008
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
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Mission Hospitals IncAsheville, North Carolina  28801
Natalie W Bryant Cancer CenterTulsa, Oklahoma  74136
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
East Carolina UniversityGreenville, North Carolina  27858
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
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Southern Illinois UniversitySpringfield, Illinois  62702
University Of Missouri-ColumbiaColumbia, Missouri  65212
Walter Reed National Military Medical CenterBethesda, Maryland  20889
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
Saint Mary's HospitalWest Palm Beach, Florida  33407
Children's Hospital and Medical Center of OmahaOmaha, Nebraska  68114
Saint Joseph's Regional Medical CenterPaterson, New Jersey  07503
Texas Tech University Health Science Center-AmarilloAmarillo, Texas  79106
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
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
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
Saint Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134
Greenville Cancer Treatment CenterGreenville, South Carolina  29605
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134
T C Thompson Children's HospitalChattanooga, Tennessee  37403
Carilion Clinic Children's HospitalRoanoke, Virginia  24014
Providence Sacred Heart Medical Center and Children's HospitalSpokane, Washington  99204
The Steven and Alexandra Cohen Children's Medical Center of New YorkNew Hyde Park, New York  11040