Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia



Status:Recruiting
Conditions:Chronic Pain, Cognitive Studies, Cognitive Studies, Other Indications, Blood Cancer, Neurology, Leukemia
Therapuetic Areas:Musculoskeletal, Neurology, Oncology, Psychiatry / Psychology, Other
Healthy:No
Age Range:1 - 30
Updated:4/21/2016
Start Date:February 2012

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A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Testing Clofarabine (NSC# 606869) in the Very High Risk Stratum

This randomized phase III trial is studying how well combination chemotherapy works in
treating young patients with newly diagnosed acute lymphoblastic leukemia that is likely to
come back or spread. Drugs used in chemotherapy work in different ways to stop the growth of
cancer cells, either by killing the cells or by stopping them from dividing. Giving more
than one drug (combination chemotherapy) and giving the drugs in different doses and in
different combinations may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To determine if the administration of post-Induction age-adjusted intrathecal triple
therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance (IM)
high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of
children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted
intrathecal (IT) methotrexate (MTX).

II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing
regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young
adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that
contains a second IM (Control Arm).

SECONDARY OBJECTIVES:

I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to
age-adjusted IT MTX in children with HR B-ALL.

II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control
Arm in children, adolescents, and young adults with VHR B-ALL.

III. To determine whether a single-arm, modified Induction with limited anthracycline
exposure and post-Induction therapy regimen with MBFM-IMIDM and reduced vincristine
(vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with
Down syndrome (DS) and HR B-ALL will result in a >= 65% 5-year DFS and < 10% Induction
mortality.

IV. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR
B-ALL.

V. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and
b) VHR B-ALL patients.

VI. To determine the incidence of osteonecrosis (ON), defined by magnetic resonance (MR)
imaging, and to characterize the natural history of clinically silent ON in children,
adolescents, and young adults 10 years of age and greater and to assess the role of drugs
(i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for
development of ON.

VII. To determine if the prevalence of cognitive deficits measured by CogState, in children
(ages 6 to 11 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher
than the normative population (> 14%) in the following domains: working memory, executive
function, visual motor, processing speed, and visual attention.

TERTIARY OBJECTIVES:

I. To determine if the reduction of minimal residual disease (MRD) from end-Induction to
end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL
receiving Experimental Arm 1 compared to the Control Arm.

OUTLINE:

INDUCTION THERAPY:

Patients without Down syndrome receive induction chemotherapy comprising cytarabine
intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) over 1 minute on days 1,
8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22;
dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old)
or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV
over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 (plus days 15 and 22 for CNS3
patients). Treatment continues for 56 days in the absence of disease progression or
unacceptable toxicity.

CONSOLIDATION THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM I HR B-ALL CONSOLIDATION (C): Patients receive consolidation therapy comprising
cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or
subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD)
on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV
over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and
43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy
(RT) QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues
for 56 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL C: Patients receive Consolidation therapy as in Arm I HR B-ALL C. Patients
also receive ITT comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on
days 1, 8, 15, and 22. Patients with testicular leukemia also undergo RT as in Arm I HR
B-ALL C.

INTERIM MAINTENANCE THERAPY:

ARM I HR B-ALL INTERIM MAINTENANCE (IM): Patients receive IM therapy comprising vincristine
sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours
on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46;
methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues
for 63 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in Arm I HR-ALL
IM. Treatment continues for 63 days in the absence of disease progression or unacceptable
toxicity.

DELAYED INTENSIFICATION THERAPY:

ARM I HR B-ALL DELAYED INTENSIFICATION (DI): Patients receive DI therapy comprising
vincristine sulfate IV over 1 hour on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID
on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15;
methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43;
cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on
days 29-32 and 36-39; and thioguanine PO QD on days 29-42. Treatment continues for 56 days
in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in Arm I HR
B-ALL DI.

MAINTENANCE (M) THERAPY:

ARM I HR B-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV
over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4);
prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not
tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15,
22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years
(females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and
maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years
(females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

VERY HIGH-RISK B-ALL: Patients are randomized to 1 of 3 treatment arms.

CONSOLIDATION THERAPY PART I: In all arms, patients receive cyclophosphamide IV over 30-60
minutes on day 1; cytarabine IV or SC on days 1-4 and 8-11; mercaptopurine PO QD on days
1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients);
vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours
on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT QD,
5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 28
days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY PART II:

ARM A VHR B-ALL C (CONTROL ARM): Patients receive consolidation therapy comprising
cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on
days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1
minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues
for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL C (EXPERIMENTAL ARM): Patients receive consolidation therapy comprising
cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on
days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over
1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression
or unacceptable toxicity.

ARM C VHR B-ALL C: Patients receive clofarabine IV over 2 hours on days 29-33 and
consolidation therapy as in Arm B VHR B-ALL C. (Closed as of 9/12/2014)

INTERIM MAINTENANCE I: In all arms, patients receive vincristine sulfate IV over 1 minute on
days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43;
leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on
days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the
absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART I: In all arms, patients receive vincristine sulfate IV over 1
minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin
hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on day 1; and
pegaspargase IV over 1-2 hours on day 4. Treatment continues for 28 days in the absence of
disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART II:

ARM A VHR B-ALL DI (CONTROL ARM): Patients receive DI therapy comprising cyclophosphamide IV
over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and
36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine
sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43.
Treatment continues for 28 days in the absence of disease progression or unacceptable
toxicity.

ARM B VHR B-ALL DI (EXPERIMENTAL ARM): Patients receive DI therapy comprising
cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on
days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days
43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in
the absence of disease progression or unacceptable toxicity.

ARM C VHR B-ALL DI: Patients receive clofarabine IV over 2 hours on days 29-33 and DI
therapy as in Arm II B VHR B-ALL DI. (Closed as of 9/12/2014)

INTERIM MAINTENANCE II: In all arms, patients receive vincristine sulfate IV over 1 minute
and methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11,
21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days
1 and 31. Treatment continues for 56 days in the absence of disease progression or
unacceptable toxicity.

MAINENTANCE THERAPY: Patients with CNS3 disease at diagnosis undergo RT QD over 4 weeks (10
fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days
1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61 (may receive
methylprednisolone IV if PO is not tolerated); methotrexate PO on days 8, 15, 22, 29, 36,
43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO QD on days
1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not
undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in
the absence of disease progression or unacceptable toxicities.

INDUCTION THERAPY: All patients receive cytarabine IT on day 1; vincristine sulfate IV over
1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or
prednisone PO BID (patients at least 10 years old) on days 1-14 (may receive
methylprednisolone IV if PO is not tolerated), pegaspargase IV over 1-2 hours on day 4;
methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Treatment continues for
14 days in the absence of disease progression or unacceptable toxicity.

Rapid early responders (RER): Patients receive induction therapy comprising vincristine
sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID or prednisone PO BID on
days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and
leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). Treatment
continues for 14 days in the absence of disease progression or unacceptable toxicity.

Slow early responders (SER): Patients receive daunorubicin hydrochloride IV over 1-15
minutes on day 15 and Induction therapy as RER patients. Treatment continues for 14 days in
the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: All patients receive cyclophosphamide IV over 30-60 minutes on days 1
and 29; cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39;
mercaptopurine PO QD on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days
15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on
days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); and leucovorin calcium PO on
days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular
leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total).
Treatment continues for 56 days in the absence of disease progression or unacceptable
toxicity.

INTERIM MAINTENANCE THERAPY: Patients receive vincristine sulfate IV over 1 minute on days
1, 15, 29, and 43; intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and
43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD
on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the
absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on
days 1, 8, 15, 43, and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin
hydrochloride IV over 1-60 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on
days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO QD on days
29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on
days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39.

MAINTENANCE THERAPY: Patients with CNS3 disease undergo RT QD, 5 days a week, for 2 weeks
(10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1;
prednisone PO BID or IV on days 1-5 (may receive methylprednisolone IV if PO not tolerated);
methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO QD
on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who
did not undergo RT). Treatment repeats every 12 weeks for 2 years in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 10 years.

Inclusion Criteria:

- Patients must be enrolled on AALL08B1 prior to enrollment on AALL1131

- White Blood Cell Count (WBC) Criteria

- Age 1-9.99 years: WBC >= 50 000/uL

- Age 10-30.99 years: Any WBC

- Age 1-30.99 years: Any WBC with:

- Testicular leukemia

- CNS leukemia (CNS3)

- Steroid pretreatment

- Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health
Organization [WHO] classification) (also termed B-precursor acute lymphoblastic
leukemia); patients with Down syndrome are also eligible

- Eligibility criteria for the Incidence and Natural History of Osteonecrosis study

- Patients must be 10 years of age or greater at the time of B-ALL diagnosis,
enrolled on AALL1131

- Patients with Down syndrome are not eligible

- Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive
Functioning study

- Patients must be aged 6 to 11 years at time of B-ALL diagnosis, enrolled on
AALL1131

- Patients must be English-, French- or Spanish-speaking (languages in which the
assessment is available)

- Patients must have no known history of neurodevelopmental disorder prior to
diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental
retardation)

- Patients must have no significant visual impairment that would prevent computer
use and recognition of the visual test stimuli

- Eligibility criteria for the National Cancer Institute (NCI) standard risk patients
from AALL0932 enrolling on this study at the end of Induction:

- Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria
will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the HR
B-ALL stratum of this study at the end of Induction:

- Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with
day 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 BM
MRD < 0.01%

- With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day
8 PB MRD and day 29 bone marrow (BM) MRD >= 0.01%

- Both NCI standard risk (SR) and HR patients without Down syndrome and with
testicular disease at diagnosis, who do not meet other VHR criteria, will be
eligible for the HR stratum

- Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria
will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the
VHR B-ALL stratum of this study at the end of Induction:

- Intrachromosomal amplification of chromosome 21 (iAMP21)

- Mixed-lineage leukemia (MLL) rearrangement

- Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index <
0.81)

- Induction failure (M3 BM at day 29)

- Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with
day 29 BM MRD >= 0.01%

- Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria
will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS
HR B-ALL stratum of this study at the end of Induction:

- Day 29 MRD >= 0.01%

- MLL rearrangement

- Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)

- DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction
failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for
post-Induction therapy on either trial (AALL0932 or AALL1131)

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met

Exclusion Criteria:

- With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for
either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation
of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed
after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving
prior steroid therapy may be eligible for AALL1131

- Patients with breakpoint cluster region (BCR)-v-abl Abelson murine leukemia viral
oncogene homolog 1 (ABL1) fusion (not eligible for post-Induction therapy on this
study; non-DS patients may be eligible to enroll in AALL1122 or successor Children's
Oncology Group [COG] Philadelphia positive [Ph+] ALL trial by day 15 Induction)

- DS HR B-ALL patients with Induction failure or BCR-ABL1

- Female patients who are pregnant are ineligible

- Lactating females are not eligible unless they have agreed not to breastfeed their
infant

- Female patients of childbearing potential are not eligible unless a negative
pregnancy test result has been obtained

- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation
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524 South Park Street
Kalamazoo, Michigan 49007
(269) 341-7654
Principal Investigator: Jeffrey S. Lobel
Phone: 800-227-2345
Bronson Methodist Hospital Our healthcare system serves patients and families throughout southwest Michigan and northern...
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2401 Gillham Rd
Kansas City, Missouri 64108
(816) 234-3000
Principal Investigator: Maxine L. Hetherington
Phone: 816-234-3265
Children's Mercy Hospital Children's Mercy Hospitals and Clinics continues redefining pediatric medicine throughout the Midwest...
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1800 West Charleston Boulevard
Las Vegas, Nevada 89102
(702) 383-2000
Principal Investigator: Jonathan Bernstein
Phone: 702-384-0013
University Medical Center of Southern Nevada University Medical Center is dedicated to providing the highest...
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529 West Markham Street
Little Rock, Arkansas 72205
(501) 686-7000
University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) in...
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Little Rock, AR
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4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Principal Investigator: Leo Mascarenhas
Phone: 323-361-4110
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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Los Angeles, CA
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8700 Beverly Blvd # 8211
Los Angeles, California 90048
(1-800-233-2771)
Principal Investigator: Fataneh (Fae) Majlessipour
Phone: 310-423-8965
Cedars Sinai Med Ctr Cedars-Sinai is known for providing the highest quality patient care. Our...
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Los Angeles, CA
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231 E Chestnut St
Louisville, Kentucky 40202
(502) 629-6000
Principal Investigator: Kenneth G. Lucas
Phone: 866-530-5516
Kosair Children's Hospital For more than a century, Kosair Children's Hospital and its predecessor hospitals...
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Louisville, KY
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4015 22nd Place
Lubbock, Texas 79410
806-725-0000
Principal Investigator: Latha Prasannan
Phone: 806-725-8000
Covenant Children's Hospital Every child is different. And when they're sick or injured, they deserve...
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Lubbock, TX
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9300 Valley Children's Pl
Madera, California 93720
(559) 353-3000
Principal Investigator: Vonda L. Crouse
Phone: 866-353-5437
Children's Hospital Central California The Children's Hospital Central California is a not-for-profit, state-of-the-art children’s hospital...
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Madera, CA
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1 Gustave L Levy Pl # 271
New York, New York 10029
 (212) 241-6500
Principal Investigator: Birte Wistinghausen
Phone: 212-824-7320
Mount Sinai Med Ctr Founded in 1852, The Mount Sinai Hospital is a 1,171-bed, tertiary-care...
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New York, NY
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601 Children's Lane
Norfolk, Virginia 23507
(757) 668-7000
Principal Investigator: Eric J. Lowe
Phone: 757-668-7243
Children's Hospital of The King's Daughters Children
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747 52nd St
Oakland, California 94609
(510) 428-3000
Principal Investigator: Carla B. Golden
Phone: 510-450-7600
Children's Hospital and Research Center Oakland For nearly 100 years, Children's Hospital & Research Center...
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Oakland, CA
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1201 W La Veta Ave
Orange, California 92868
(714) 997-3000
Principal Investigator: Violet Shen
Phone: 714-997-3000
Children's Hospital of Orange County For more than 45 years, CHOC Children’s has been steadfastly...
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Orange, CA
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1717 South Orange Avenue # 100
Orlando, Florida 32806
(407) 650-7000
Nemours Children's Clinic - Orlando Located near downtown Orlando, Nemours Children’s Clinic, Orlando is a...
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Orlando, FL
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5153 North 9th Avenue
Pensacola, Florida 32504
(850) 505-4700
Principal Investigator: Jeffrey H. Schwartz
Phone: 904-697-3529
Nemours Children's Clinic - Pensacola Nemours Children’s Clinic, Pensacola serves children and families in northwest...
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530 Northeast Glen Oak Avenue
Peoria, Illinois 61603
(309) 624-4945
Principal Investigator: Karen S. Fernandez
Phone: 309-655-3258
Saint Jude Midwest Affiliate The Jim and Trudy Maloof St. Jude Midwest Affiliate Clinic was...
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Peoria, IL
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Principal Investigator: Susan R. Rheingold
Phone: 215-590-2810
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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4401 Penn Avenue
Pittsburgh, Pennsylvania 15224
412-692-5325
Principal Investigator: Arthur K. Ritchey
Phone: 412-692-5573
Children's Hospital of Pittsburgh of UPMC UPMC is one of the leading nonprofit health systems...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Principal Investigator: Bill H. Chang
Phone: 503-494-1080
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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Portland, OR
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620 John Paul Jones Cir
Portsmouth, Virginia 23708
(757) 953-5008
Principal Investigator: Bethany M. Mikles
Phone: 757-953-5939
Naval Medical Center - Portsmouth Naval Medical Center Portsmouth, Virginia has proudly served the military...
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Portsmouth, VA
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593 Eddy Street
Providence, Rhode Island 02903
401-444-4000
Principal Investigator: Jennifer J. Greene Welch
Phone: 401-444-1488
Rhode Island Hospital Founded in 1863, Rhode Island Hospital in Providence, RI, is a private,...
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401 College Street
Richmond, Virginia 23298
(804) 828-0450
Principal Investigator: Christina M. Wiedl
Phone: 804-628-1939
Virginia Commonwealth University Massey Cancer Center Founded in 1974, VCU Massey Cancer Center is a...
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Richmond, VA
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60 Crittenden Blvd # 70
Rochester, New York 14642
(585) 275-2121
Principal Investigator: Jeffrey R. Andolina
Phone: 585-275-5830
University of Rochester The University of Rochester is one of the country's top-tier research universities....
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Rochester, NY
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7700 Floyd Curl Dr
San Antonio, Texas 78229
(210) 575-7000
Principal Investigator: Gerardo Quezada
Phone: 888-823-5923
Methodist Children's Hospital of South Texas Methodist Children
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4502 Medical Drive
San Antonio, Texas 78284
(210) 567-7000
Principal Investigator: Anne-Marie R. Langevin
Phone: 210-450-3800
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
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San Antonio, TX
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3020 Childrens way
San Diego, California 92123
(858) 576-1700
Principal Investigator: William D. Roberts
Phone: 858-966-5934
Rady Children's Hospital - San Diego Rady Children's Hospital-San Diego is the region’s pediatric medical...
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34800 Bob Wilson Dr,
San Diego, California 92134
(619) 532-6400
Principal Investigator: Shelton A. Viola
Phone: 619-532-8712
Naval Medical Center - San Diego We are the largest and most comprehensive military healthcare...
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1 Tampa General Cir
Tampa, Florida 33606
(813) 844-7000
Principal Investigator: Cameron K. Tebbi
Phone: 800-882-4123
Tampa General Hospital In a diverse city known for its rich culture and beautiful beaches,...
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40 Sunshine Cottage Road
Valhalla, New York 10595
(914) 594-4000
Principal Investigator: Jessica C. Hochberg
Phone: 914-594-3794
New York Medical College The College was founded in 1860 by a group of New...
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Valhalla, NY
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1600 Rockland Road
Wilmington, Delaware 19803
(302) 651-4200
Principal Investigator: Jeffrey H. Schwartz
Phone: 904-697-3529
Alfred I. duPont Hospital for Children Nemours began more than 70 years ago with the...
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Wilmington, DE
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Akron, Ohio 44308
Principal Investigator: Steven J. Kuerbitz
Phone: 330-543-3193
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Akron, OH
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Albany, New York 12208
Principal Investigator: Vikramjit S. Kanwar
Phone: 518-262-3368
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Albany, NY
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Amarillo, TX
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Anchorage, Alaska 99508
Principal Investigator: Brenda J. Wittman
Phone: 907-261-3109
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Anchorage, AK
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1540 East Hospital Drive
Ann Arbor, Michigan 48109
(877) 475-6688
Principal Investigator: Raymond J. Hutchinson
Phone: 800-865-1125
C S Mott Children's Hospital Behind the doors of C.S. Mott Children's Hospital there exist...
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Ann Arbor, MI
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Atlanta, Georgia 30322
Principal Investigator: Glen Lew
Phone: 404-785-1112
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Atlanta, GA
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Augusta, Georgia 30912
Principal Investigator: Colleen H. McDonough
Phone: 706-721-1663
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Augusta, GA
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13123 E 16th Ave
Aurora, Colorado 80045
(720) 777-1234
Principal Investigator: Kelly W. Maloney
Phone: 720-777-6672
Children's Hospital Colorado At Children's Hospital Colorado, we see more, treat more and heal more...
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22 South Greene Street
Baltimore, Maryland 21201
410-328-7904
Principal Investigator: Teresa A. York
Phone: 800-888-8823
University of Maryland Greenebaum Cancer Center The University of Maryland Marlene and Stewart Greenebaum Cancer...
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Baltimore, MD
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2401 W Belvedere Ave
Baltimore, Maryland 21215
(410) 601-9000
Principal Investigator: Joseph M. Wiley
Phone: 410-601-6120
Sinai Hospital of Baltimore Sinai Hospital of Baltimore provides a broad array of high-quality, cost-effective...
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Baltimore, MD
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401 North Broadway
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Patrick A. Brown
Phone: 410-955-8804
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
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Baltimore, MD
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489 State St
Bangor, Maine 04401
(207) 973-7000
Principal Investigator: Sam W. Lew
Phone: 207-973-4274
Eastern Maine Medical Center Located in Bangor, Eastern Maine Medical Center (EMMC) serves communities throughout...
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Bangor, ME
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8901 Rockville Pike
Bethesda, Maryland 20889
(301) 295-4000
Principal Investigator: Anne B. Warwick
Phone: 301-319-2100
Walter Reed National Military Medical Center The Walter Reed National Military Medical Center is one...
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Bethesda, MD
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Birmingham, AL
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100 E Idaho St
Boise, Idaho 83712
(208) 381-2711
Principal Investigator: Eugenia Chang
Phone: 800-845-4624
Saint Luke's Mountain States Tumor Institute For more than 100 years, St. Luke
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Boise, ID
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Boston, Massachusetts 02111
Principal Investigator: Michael J. Kelly
Phone: 617-636-5000
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Boston, MA
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55 Fruit St
Boston, Massachusetts 02114
(617) 724-4000
Principal Investigator: Howard Weinstein
Phone: 212-639-7202
Massachusetts General Hospital Cancer Center An integral part of one of the world
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Boston, MA
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Bronx, New York 10467
Principal Investigator: Peter D. Cole
Phone: 718-904-2730
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Bronx, NY
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Chapel Hill, North Carolina 27599
Principal Investigator: Stuart H. Gold
Phone: 877-668-0683
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Chapel Hill, NC
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Principal Investigator: Jacqueline M. Kraveka
Phone: 843-792-9321
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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Charleston, SC
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Charleston, West Virginia 25304
Principal Investigator: Chibuzo C. O'Suoji
Phone: 304-388-9944
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Charleston, WV
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Charlotte, North Carolina 28204
Principal Investigator: Joel A. Kaplan
Phone: 704-381-9901
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Charlotte, NC
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Charlotte, North Carolina 28204
Principal Investigator: Paulette C. Bryant
Phone: 704-384-5369
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Charlotte, NC
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Chattanooga, Tennessee 37403
Principal Investigator: Manoo G. Bhakta
Phone: 423-778-7289
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Chicago, Illinois 60614
Principal Investigator: Elaine R. Morgan
Phone: 773-880-4562
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Chicago, IL
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1200 West Harrison Stree
Chicago, Illinois 60607
(312) 996-4350
Principal Investigator: Mary L. Schmidt
Phone: 312-355-3046
Univ of Illinois A major research university in the heart of one of the world's...
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Chicago, IL
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5841 S Maryland Ave
Chicago, Illinois 60637
1-773-702-6180
Principal Investigator: Susan L. Cohn
Phone: 773-834-7424
University of Chicago Comprehensive Cancer Center The University of Chicago Comprehensive Cancer Center (UCCCC) is...
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Chicago, IL
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2049 E 100th St
Cleveland, Ohio 44106
(216) 444-2200
Principal Investigator: Aron Flagg
Phone: 866-223-8100
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
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Cleveland, OH
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Columbia, Missouri 65201
Principal Investigator: Thomas W. Loew
Phone: 573-884-4277
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Columbia, MO
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1 Hospital Dr
Columbia, Missouri 65212
(573) 882-2100
University of Missouri-Ellis Fischel Ellis Fischel Cancer Center's team of physician specialists and other trained...
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Columbia, MO
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5 Richland Medical Park Dr
Columbia, South Carolina 29203
(803) 434-7000
Principal Investigator: Ronnie W. Neuberg
Phone: 803-434-3680
Palmetto Health Richland Palmetto Health Richland, originally founded in 1892 as Columbia Hospital, has a...
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Dallas, Texas 75390
Principal Investigator: Tamra L. Slone
Phone: 214-648-7097
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100 North Academy Avenue
Danville, Pennsylvania 17822
570-271-6211
Principal Investigator: Jagadeesh Ramdas
Phone: 570-271-5251
Geisinger Medical Center Since 1915, Geisinger Medical Center has been known as the region’s resource...
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Danville, PA
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Dayton, Ohio 45404
Principal Investigator: Ayman A. El-Sheikh
Phone: 800-237-1225
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Dayton, OH
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Denver, Colorado 80218
Principal Investigator: Jennifer J. Clark
Phone: 866-775-6246
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4160 John R St #2122
Detroit, Michigan 48201
(313) 833-1785
Principal Investigator: Zhihong J. Wang
Phone: 313-576-9363
Wayne State University/Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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Detroit, MI
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22101 Moross Rd
Detroit, Michigan 48236
(313) 343-4000
Principal Investigator: Hadi Sawaf
Phone: 313-343-3166
Saint John Hospital and Medical Center Founded in 1952, St. John Hospital and Medical Center...
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Detroit, MI
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4760 Sunset Blvd
Downey, California 90027
(323) 783-6151
Principal Investigator: Robert M. Cooper
Phone: 626-564-3455
Southern California Permanente Medical Group We
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2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Principal Investigator: Susan G. Kreissman
Phone: 888-275-3853
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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Durham, NC
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East Lansing, Michigan 48824
Principal Investigator: Renuka Gera
Phone: 517-975-9547
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El Paso, Texas 79905
Principal Investigator: Lisa L. Hartman
Phone: 888-823-5923
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801 Broadway
Fargo, North Dakota 58102
(701) 234-6175
Principal Investigator: Samuel O. Anim
Phone: 701-234-6161
Sanford Medical Center-Fargo Sanford Medical Center Fargo is a major medical center that provides comprehensive,...
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Fargo, ND
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1600 S Andrews Ave
Fort Lauderdale, Florida 33316
(954) 355-4400
Principal Investigator: Hector M. Rodriguez-Cortes
Phone: 954-355-5346
Broward Health Medical Center Broward Health, providing service for more than 75 years, is a...
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Fort Myers, Florida 33908
Principal Investigator: Emad K. Salman
Phone: 239-343-5333
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Fort Myers, FL
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801 7th Avenue
Fort Worth, Texas 76104
(682) 885-4000
Principal Investigator: Kenneth M. Heym
Phone: 682-885-2103
Cook Children's Medical Center Cook Children's Health Care System is a not-for-profit, nationally recognized pediatric...
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Fort Worth, TX
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835 S Van Buren St
Green Bay, Wisconsin 54301
(920) 433-0111
Principal Investigator: John R. Hill
Phone: 920-433-8889
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1001 E 5th St
Greenville, North Carolina 27858
(252) 328-6131
Principal Investigator: George E. Hucks
Phone: 252-744-2391
East Carolina University Whether it's meeting the demand for more teachers and healthcare professionals or...
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Greenville, NC
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