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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActive1 to 30NCI, OtherAALL1131
NCI-2011-03797, CDR0000706370, U10CA098543, COG-AALL1131, NCT01406756

Trial Description

Summary

This randomized phase III trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed high-risk acute lymphoblastic leukemia. 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.

Further Study Information

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) 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) or the clofarabine + cyclophosphamide + etoposide-combination regimen (Experimental Arm 2) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm).

III. To determine, in a randomized fashion, if the cyclophosphamide + etoposide + clofarabine-containing combination regimen (Experimental Arm 2) will improve the 4-year DFS of children, adolescents, and young adults with VHR-ALL compared to the cyclophosphamide + etoposide combination regimen (Experimental Arm 1).

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-ALL.

II. To determine the toxicity and tolerability of Experimental Arms 1 and 2 compared to the Control Arm in children, adolescents, and young adults with VHR-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/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality, and to gather clinical and biologic data that will facilitate further study to improve outcomes for this biologically and clinically unique patient subgroup.

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

V. 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-ALL receiving Experimental Arms 1 and/or 2 compared to the Control Arm.

VI. To estimate overall survival (OS) rates both overall and by regimen for HR-ALL and VHR-ALL patients.

VII. To determine if peripheral blood absolute lymphocyte count (ALC) at day 29 of Induction is predictive of DFS in children, adolescents, and young adults with HR-ALL.

VIII. To determine the incidence and prognostic significance of recently discovered recurrent genomic lesions, including high cytokine receptor-like factor 2 (CRLF2) expression, CRLF2-activating genomic lesions, janus kinase (JAK) mutations, and IKAROS family zinc finger 1 (Ikaros) (IKZF1) mutations/deletions, in patients treated on this trial.

IX. To determine the prognostic significance of molecular risk classifiers using Low Density Array (LDA) Taqman cards.

X. To define the frequency of occurrence of key adverse events across all patient subgroups of HR-ALL in order to provide data for linked correlative biology studies that seek to develop biomarkers predictive of patients at risk for such events, including the following specific events: Grade 2 or higher (CNS hemorrhage, pancreatitis, osteonecrosis [ON], and seizure), Grade 3 or higher (GI bleed, encephalopathy, neuropathy, allergic reaction, ileus, mucositis/stomatitis, hyperbilirubinemia, and thrombosis), and all grades (transient ischemic attacks, strokes).

XI. To define the differences in the burden of therapy between HR-ALL and VHR-ALL when treated on the various arms of this study by collecting and comparing the total number of days admitted to the hospital.

XII. To determine the incidence of 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.

XIII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to 11 years) with HR- and VHR-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.

XIV. To compare the drug delivery of vincristine, pegaspargase, and methotrexate during Induction, Consolidation, Delayed Intensification, and Interim Maintenance II in 16-30 year olds treated on the control arm of the VHR study to that of adolescents and young adults (AYAs) with ALL treated with the same therapy on the C10403 adult cooperative group trial.

OUTLINE: This is a multicenter study. Patients are stratified according to Down syndrome (no vs yes).

Induction therapy for ALL patients without Down syndrome (35 days): Patients 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 are stratified according to National Cancer Institute (NCI) ALL risk criteria (high-risk or standard-risk vs very high-risk). High-risk or standard-risk ALL: Patients are randomized to 1 of 2 treatment arms.

Consolidation therapy (56 days):

Arm I HR-ALL C: Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-4 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) once daily, 5 days a week, for approximately 2½ weeks (12 fractions total).

Arm II HR-ALL C: Patients receive intrathecal triple therapy (ITT) comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients also receive consolidation therapy as patients in arm I HR-ALL C. Patients with testicular leukemia also undergo RT as in arm I HR-ALL C.

Interim maintenance therapy (63 days):

Arm I HR-ALL IM: Patients receive interim maintenance (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.

Arm II HR-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in arm I HR-ALL IM.

Delayed intensification therapy (56 days):

Arm I HR-ALL DI: Patients receive delayed intensification (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 1-15 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 on days 29-42.

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

Maintenance therapy:

Arm I HR-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on days 1 (also day 29 of courses 1-4) ; prednisone PO BID or IV on days 1-5, 29-33, and 57-61; mercaptopurine PO 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-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in arm I HR-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 ALL: Patients are randomized to 1 of 3 treatment arms.

Consolidation therapy part 1 (days 1-28): 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 on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS 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 once daily, 5 days a week, for approximately 2½ weeks (12 fractions total).

Consolidation therapy part 2 (days 29-57):

Arm A VHR-ALL C: Patients receive consolidation 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; mercaptopurine PO 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.

Arm B VHR-ALL C: Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 1-2 hours 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.

Arm C VHR-ALL C: Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in arm B VHR-ALL C.

Interim Maintenance I (63 days): 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 on days 1-56; and methotrexate IT on days 1 and 29.

Delayed Intensification part 1 (days 1-28): 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 1-15 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4.

Delayed Intensification part 2 (days 29-57):

Arm A VHR-ALL DI: 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 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.

Arm B VHR-ALL DI: Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 1-2 hours 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.

Arm C VHR-ALL DI: Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in arm II B VHR-ALL DI.

Interim Maintenance II (56 days): In all arms, patients receive vincristine sulfate IV over 1 minute and methotrexate IV 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.

Maintenance therapy: Patients with CNS3 disease at diagnosis undergo RT once daily 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; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not receive RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

High-risk ALL patients with Down syndrome: Patients are stratified according to response to induction therapy (days 1-14) (rapid early responders [RER; M1 day 15 bone marrow] vs slow early responders [SER; M2/M3 day 15 bone marrow]).

Induction therapy (days 1-14): 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, pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11.

Induction therapy (day 15-29): 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). SER patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and induction therapy as RER patients.

Consolidation therapy (56 days): 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 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; 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 once daily, 5 days a week, for approximately 2½ weeks (12 fractions total).

Interim maintenance therapy (63 days): Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; 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 on days 1-56; and methotrexate IT on days 1 and 29.

Delayed intensification therapy: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 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 on days 29-42; cytarabine IV over 15-30 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 once daily, 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; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not receive RT). Treatment repeats every 12 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Patients undergo peripheral blood and bone marrow collection for correlative studies. Patients who are at least 10 years old have MRIs during Consolidation, Maintenance, and End of therapy and blood draws during Consolidation, Delayed Intensification, and Interim Maintenance II (VHR-ALL only). Patients may also undergo neurocognitive assessment during consolidation therapy, periodically during maintenance therapy, and at 1 year after completion of study therapy.

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

Eligibility Criteria

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/μL
  • 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 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
  • 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 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 BM MRD > 0.01%
  • Both NCI 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:
  • 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 BCR-ABL1 fusion (not eligible for post-Induction therapy on this study; non-DS patients may be eligible to enroll in AALL1122 or successor COG Ph+ ALL trial by Day 15 Induction)
  • DS HR B-ALL patients with Induction failure or BCR-ABL1
  • Direct bilirubin > 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) > 3 x upper limit of normal (ULN) for age
  • Lipase > 2.0 x upper limit of normal (ULN) for age
  • Creatinine clearance or radioisotope GFR < 70 mL/min/1.73 m^2
  • A serum creatinine based on age/gender as follows:
  • 1 month to < 6 months = 0.4 (male) and 0.4 (female)
  • 6 months to < 1 year = 0.5 (male) and 0.5 (female)
  • 1 to < 2 years = 0.6 (male) and 0.6 (female)
  • 2 to < 6 years = 0.8 (male) and 0.8 (female)
  • 6 to < 10 years = 1 (male) and 1 (female)
  • 10 to < 13 years = 1.2 (male) and 1.2 (female)
  • 13 to < 16 years = 1.5 (male) and 1.4 (female)
  • >= 16 years = 1.7 (male) and 1.4 (female)
  • VHR B-ALL patients with known Hepatitis B or C infection or history of cirrhosis at the time of post-Induction randomization
  • Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs
  • 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

  • National Cancer Institute
Michael Burke, MD, Principal Investigator

Trial Sites

U.S.A.

Alabama
Birmingham

Children's Hospital of Alabama at University of Alabama at Birmingham

Alyssa T Reddy
Ph: 205-934-0309

Mobile

University of South Alabama Mitchell Cancer Institute

Felicia L Wilson
Ph: 251-665-8000

Alaska
Anchorage

Providence Cancer Center

Brenda J Wittman
Ph: 907-261-3109

Arizona
Mesa

Cardon Children's Medical Center

Xiaxin Li
Ph: 602-747-9738

Phoenix

Phoenix Children's Hospital

Jessica Boklan
Ph: 602-546-0920

Tucson

Arizona Cancer Center at University of Arizona Health Sciences Center

Lisa M Kopp
Ph: 520-626-9008

Arkansas
Little Rock

Arkansas Children's Hospital at the University of Arkansas for Medical Sciences

David L Becton
Ph: 501-364-7373

California
Downey

Southern California Permanente Medical Group

Robert M Cooper
Ph: 626-564-3455

Duarte

City of Hope Comprehensive Cancer Center

Michael J Burke

Loma Linda

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Antranik A Bedros
Ph: 909-558-3375

Long Beach

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

Theodore Zwerdling
Ph: 562-933-5600

Los Angeles

Children's Hospital Los Angeles

Leo Mascarenhas
Ph: 323-361-4110

Mattel Children's Hospital at UCLA

Pamela H Kempert
Ph: 310-825-6708

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Fataneh (Fae) Majlessipour
Ph: 310-423-8965

Madera

Children's Hospital Central California

Vonda L Crouse
Ph: 866-353-5437

Oakland

Children's Hospital and Research Center Oakland

Carla B Golden
Ph: 510-450-7600

Kaiser Permanente-Oakland

Steven K Bergstrom
Ph: 626-564-3455

Orange

Children's Hospital of Orange County

Violet Shen
Ph: 714-997-3000

Palo Alto

Lucile Packard Children's Hospital at Stanford University Medical Center

Neyssa M Marina
Ph: 650-498-7061
Email: clinicaltrials@med.stanford.edu

Sacramento

Sutter Cancer Center

Yung S Yim
Ph: 415-209-2686
Email: bernicl@sutterhealth.org

University of California Davis Cancer Center

Jay Michael S Balagtas
Ph: 916-734-3089

San Diego

Rady Children's Hospital - San Diego

William D Roberts
Ph: 858-966-5934

San Francisco

UCSF Helen Diller Family Comprehensive Cancer Center

Mignon Loh
Ph: 877-827-3222

Santa Barbara

Santa Barbara Cottage Hospital

Daniel J Greenfield
Ph: 805-682-7300

Torrance

Los Angeles Biomedical Research Institute

Joseph L Lasky
Ph: 888-662-8252

Colorado
Aurora

Children's Hospital Colorado Center for Cancer and Blood Disorders

Kelly W Maloney
Ph: 720-777-6672

Denver

Presbyterian - St. Luke's Medical Center

Jennifer J Clark
Ph: 866-775-6246

Connecticut
Hartford

Connecticut Children's Medical Center

Michael S Isakoff
Ph: 860-545-9981

New Haven

Yale Cancer Center

Nina S Kadan-Lottick
Ph: 203-785-5702

Delaware
Wilmington

Alfred I. duPont Hospital for Children

Jeffrey H Schwartz
Ph: 904-697-3529

District of Columbia
Washington

Children's National Medical Center

Jeffrey S Dome
Ph: 202-884-2549

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Aziza T Shad
Ph: 202-444-0381

Florida
Fort Lauderdale

Broward General Medical Center Cancer Center

Hector M Rodriguez-Cortes
Ph: 954-355-5346

Fort Myers

Children's Hospital of Southwest Florida

Emad K Salman
Ph: 239-343-5333

Gainesville

UF Health Cancer Center

William B Slayton
Ph: 352-273-8675
Email: trials@cancer.ufl.edu

Hollywood

Joe DiMaggio Children's Hospital

Iftikhar Hanif
Ph: 954-265-2234

Jacksonville

Nemours Children's Clinic

Jeffrey H Schwartz
Ph: 904-697-3529

Miami

Baptist-South Miami Regional Cancer Program

Doured Daghistani
Ph: 800-599-2456
Email: cancerinfo@baptisthealth.net

Miami Children's Hospital

Enrique A Escalon
Ph: 305-662-8360

University of Miami Sylvester Comprehensive Cancer Center - Miami

Julio C Barredo
Ph: 866-574-5124
Email: Sylvester@emergingmed.com

Orlando

Arnold Palmer Hospital for Children

Vincent F Giusti
Ph: 321-841-7246
Email: CancerClinicalTrials@orlandohealth.com

Florida Hospital Cancer Institute at Florida Hospital Orlando

Fouad M Hajjar
Ph: 407-303-5623

Nemours Children's Hospital

Jeffrey H Schwartz
Ph: 904-697-3529

Pensacola

Nemours Children's Clinic - Pensacola

Jeffrey H Schwartz
Ph: 904-697-3529

Saint Petersburg

All Children's Hospital

Gregory A Hale
Ph: 727-767-2423
Email: HamblinF@allkids.org

Tampa

St. Joseph's Children's Hospital of Tampa

Dana A Obzut
Ph: 800-882-4123

West Palm Beach

Kaplan Cancer Center at St. Mary's Medical Center

Narayana Gowda
Ph: 888-823-5923
Email: ctsucontact@westat.com

Georgia
Atlanta

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Glen Lew
Ph: 404-785-1112

Augusta

Medical College of Georgia Cancer Center

Colleen H McDonough
Ph: 706-721-1663
Email: cancer@georgiahealth.edu

Savannah

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

J. M Johnston
Ph: 912-350-8568

Hawaii
Honolulu

Kapiolani Medical Center for Women and Children

Robert W Wilkinson
Ph: 808-983-6090

Tripler Army Medical Center

Jeremy V Edwards
Ph: 808-433-6336

Idaho
Boise

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Eugenia Chang
Ph: 800-845-4624

Illinois
Chicago

Ann and Robert H. Lurie Children's Hospital of Chicago

Elaine R Morgan
Ph: 773-880-4562

University of Chicago Cancer Research Center

Susan L Cohn
Ph: 773-834-7424

University of Illinois Cancer Center

Mary L Schmidt
Ph: 312-355-3046

Maywood

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Eugene Suh
Ph: 708-226-4357

Oak Lawn

Keyser Family Cancer Center at Advocate Hope Children's Hospital

Rebecca E McFall
Ph: 847-723-7570

Park Ridge

Advocate Children's Hospital-Park Ridge

Rebecca E McFall
Ph: 847-723-7570

Peoria

Saint Jude Midwest Affiliate

Karen S Fernandez
Ph: 309-655-3258

Springfield

Simmons Cooper Cancer Institute

Gregory P Brandt
Ph: 217-545-7929

Indiana
Indianapolis

Riley's Children Cancer Center at Riley Hospital for Children

Robert J Fallon
Ph: 317-274-2552

St. Vincent Indianapolis Hospital

Bassem I Razzouk
Ph: 317-338-2194

Iowa
Des Moines

Blank Children's Hospital

Wendy L Woods-Swafford
Ph: 515-241-6729

Iowa City

Holden Comprehensive Cancer Center at University of Iowa

Ayman A El-Sheikh
Ph: 800-237-1225

Kentucky
Lexington

University of Kentucky Chandler Medical Center

Lars M Wagner
Ph: 859-257-3379

Louisville

Kosair Children's Hospital

Kenneth G Lucas
Ph: 866-530-5516

Louisiana
New Orleans

Children's Hospital of New Orleans

Lolie C Yu
Ph: 504-894-5377

Ochsner Cancer Institute at Ochsner Clinic Foundation

Craig Lotterman
Ph: 888-562-4763

Maine
Bangor

CancerCare of Maine at Eastern Maine Medical Center

Sarah J Fryberger
Ph: 207-973-4274

Scarborough

Maine Children's Cancer Program at Barbara Bush Children's Hospital

Eric C Larsen
Ph: 207-396-8090
Email: wrighd@mmc.org

Maryland
Baltimore

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Joseph M Wiley
Ph: 410-601-6120
Email: pridgely@lifebridgehealth.org

Greenebaum Cancer Center at University of Maryland Medical Center

Teresa A York
Ph: 800-888-8823

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Patrick A Brown
Ph: 410-955-8804
Email: jhcccro@jhmi.edu

Massachusetts
Boston

Floating Hospital for Children at Tufts - New England Medical Center

Michael J Kelly
Ph: 617-636-5000
Email: ContactUsCancerCenter@TuftsMedicalCenter.org

Massachusetts General Hospital

Alison M Friedmann
Ph: 877-726-5130

Springfield

Baystate Medical Center

Joanna G Luty
Ph: 413-794-3565
Email: tamara.wrenn@baystatehealth.org

Worcester

UMASS Memorial Cancer Center - University Campus

Christopher P Keuker
Ph: 508-856-3216
Email: cancer.research@umassmed.edu

Michigan
Ann Arbor

C.S. Mott Children's Hospital at University of Michigan Medical Center

Raymond J Hutchinson
Ph: 800-865-1125

Detroit

Van Elslander Cancer Center at St. John Hospital and Medical Center

Hadi Sawaf
Ph: 313-343-3166

Wayne State University

Zhihong J Wang
Ph: 313-576-9363

East Lansing

Breslin Cancer Center at Ingham Regional Medical Center

Renuka Gera
Ph: 517-975-9547

Flint

Hurley Medical Center

Susumu Inoue
Ph: 888-606-6556

Grand Rapids

Helen DeVos Children's Hospital at Spectrum Health

David S Dickens
Ph: 616-267-1925

Kalamazoo

Bronson Methodist Hospital

Jeffrey S Lobel
Ph: 800-227-2345

Royal Oak

William Beaumont Hospital - Royal Oak Campus

Laura K Gowans
Ph: 248-551-7695

Minnesota
Minneapolis

Children's Hospitals and Clinics of Minnesota - Minneapolis

Bruce C Bostrom
Ph: 612-813-5193

Masonic Cancer Center at University of Minnesota

Peter M Gordon
Ph: 612-624-2620

Rochester

Mayo Clinic Cancer Center

Vilmarie Rodriguez
Ph: 507-538-7623

Mississippi
Jackson

University of Mississippi Cancer Clinic

Gail C Megason
Ph: 601-815-6700

Missouri
Kansas City

Children's Mercy Hospital

Maxine L Hetherington
Ph: 816-234-3265

Saint Louis

Cardinal Glennon Children's Hospital

William S Ferguson
Ph: 314-268-4000

David C. Pratt Cancer Center at St. John's Mercy

Bethany G. Sleckman
Ph: 913-948-5588

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Robert J Hayashi
Ph: 800-600-3606
Email: info@siteman.wustl.edu

Nebraska
Omaha

Children's Hospital

Minnie Abromowitch
Ph: 402-955-3949

Fred and Pamela Buffett Cancer Center

Minnie Abromowitch
Ph: 402-955-3949

Nevada
Las Vegas

CCOP - Nevada Cancer Research Foundation

Jonathan Bernstein
Ph: 702-384-0013

Children's Specialty Center of Nevada

Jonathan Bernstein
Ph: 702-384-0013

Sunrise Hospital and Medical Center

Nik Farahana N Rashid
Ph: 702-384-0013

University Medical Center of Southern Nevada

Jonathan Bernstein
Ph: 702-384-0013

New Hampshire
Lebanon

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Sara Chaffee
Ph: 800-639-6918
Email: cancer.research.nurse@dartmouth.edu

New Jersey
Hackensack

Hackensack University Medical Center Cancer Center

Burton E Appel
Ph: 201-996-2879

Morristown

Carol G. Simon Cancer Center at Morristown Memorial Hospital

Steven L Halpern
Ph: 973-971-5900

New Brunswick

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Richard A Drachtman
Ph: 732-235-8675

Saint Peter's University Hospital

Stanley Calderwood
Ph: 732-745-8600ext6163
Email: kcovert@saintpetersuh.com

Newark

Newark Beth Israel Medical Center

Peri Kamalakar
Ph: 973-926-7230

Paterson

St. Joseph's Hospital and Medical Center

Mary A Bonilla
Ph: 973-754-2909

Summit

Overlook Hospital

Steven L Halpern
Ph: 973-971-5900

New Mexico
Albuquerque

University of New Mexico Cancer Center

Koh B Boayue
Ph: 505-272-6972

Michael J Burke

New York
Albany

Albany Medical Center Hospital

Vikramjit S Kanwar
Ph: 518-262-3368

Bronx

Montefiore Medical Center

Peter D Cole
Ph: 718-904-2730
Email: aecc@aecom.yu.edu

Mineola

Winthrop University Hospital

Mark E Weinblatt
Ph: 866-946-8476

New Hyde Park

Schneider Children's Hospital

Arlene S Redner
Ph: 718-470-3470

New York

Mount Sinai Medical Center

Birte Wistinghausen
Ph: 212-824-7320
Email: jenny.figueroa@mssm.edu

New York University Medical Center

Linda Granowetter
Ph: 212-263-4434
Email: prmc.coordinator@nyumc.org

New York Weill Cornell Cancer Center at Cornell University

Alexander Aledo
Ph: 212-746-1848

Rochester

James P. Wilmot Cancer Center at University of Rochester Medical Center

Jeffrey R Andolina
Ph: 585-275-5830

Stony Brook

Stony Brook University Cancer Center

Robert I Parker
Ph: 800-862-2215

Syracuse

SUNY Upstate Medical University Hospital

Karol H Kerr
Ph: 315-464-5476

Valhalla

New York Medical College

Jessica C Hochberg
Ph: 914-594-3794

North Carolina
Asheville

Mission Hospitals - Memorial Campus

Douglas J Scothorn
Ph: 828-213-4150

Chapel Hill

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Stuart H Gold
Ph: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu

Charlotte

Blumenthal Cancer Center at Carolinas Medical Center

Joel A Kaplan
Ph: 704-355-2884

Presbyterian Cancer Center at Presbyterian Hospital

Paulette C Bryant
Ph: 704-384-5369

Durham

Duke Cancer Institute

Susan G Kreissman
Ph: 888-275-3853

Greenville

Leo W. Jenkins Cancer Center at ECU Medical School

George E Hucks
Ph: 252-744-2391

Winston-Salem

Wake Forest University Comprehensive Cancer Center

Thomas W McLean
Ph: 336-713-6771

North Dakota
Fargo

Roger Maris Cancer Center at MeritCare Hospital

Samuel O Anim
Ph: 701-234-6161

Ohio
Akron

Akron Children's Hospital

Steven J Kuerbitz
Ph: 330-543-3193

Cincinnati

Cincinnati Children's Hospital Medical Center

John P Perentesis
Ph: 513-636-2799

Cleveland

Cleveland Clinic Taussig Cancer Center

Margaret C Thompson
Ph: 866-223-8100

Seidman Cancer Center at University Hospitals/Case Medical Center

Yousif (Joe) H Matloub
Ph: 216-844-5437

Columbus

Nationwide Children's Hospital

Mark A Ranalli
Ph: 614-722-2708

Dayton

Dayton Children's - Dayton

Emmett H Broxson
Ph: 800-228-4055

Toledo

Mercy Children's Hospital

Rama Jasty
Ph: 419-251-8210

Toledo Hospital

Jamie L Dargart
Ph: 419-824-1842

Oklahoma
Oklahoma City

Stephenson Cancer Center at the University of Oklahoma

Rene Y McNall-Knapp
Ph: 405-271-4272
Email: julie-traylor@ouhsc.edu

Tulsa

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Gregory B Kirkpatrick
Ph: 918-494-2200

Oregon
Portland

Knight Cancer Institute at Oregon Health and Science University

Bill H Chang
Ph: 503-494-1080
Email: trials@ohsu.edu

Legacy Emanuel Children's Hospital

Janice F Olson
Ph: 503-413-2560

Pennsylvania
Bethlehem

Lehigh Valley Hospital - Muhlenberg

Philip M Monteleone
Ph: 484-884-2201

Danville

Geisinger Cancer Institute at Geisinger Health

Jagadeesh Ramdas
Ph: 570-271-5251

Hershey

Penn State Children's Hospital

Lisa M McGregor
Ph: 717-531-6012

Philadelphia

Children's Hospital of Philadelphia

Susan R Rheingold
Ph: 215-590-2810

St. Christopher's Hospital for Children

Gregory E Halligan
Ph: 215-427-8991

Pittsburgh

Children's Hospital of Pittsburgh of UPMC

Arthur K Ritchey
Ph: 412-692-5573

Rhode Island
Providence

Rhode Island Hospital Comprehensive Cancer Center

Jennifer J Greene Welch
Ph: 401-444-1488

South Carolina
Charleston

Hollings Cancer Center at Medical University of South Carolina

Jacqueline M Kraveka
Ph: 843-792-9321

Columbia

Palmetto Health South Carolina Cancer Center

Ronnie W. Neuberg
Ph: 803-434-3680

Greenville

BI-LO Charities Children's Cancer Center

Nichole L Bryant
Ph: 864-241-6251

Cancer Centers of the Carolinas - Faris Road

Cary E Stroud
Ph: 864-241-6251

South Dakota
Sioux Falls

Sanford Cancer Center at Sanford USD Medical Center

Kayelyn J Wagner
Ph: 605-328-1367

Tennessee
Chattanooga

T.C. Thompson Children's Hospital

Manoo G Bhakta
Ph: 423-778-7289

Knoxville

East Tennessee Children's Hospital

Ray C Pais
Ph: 865-541-8266

Nashville

Vanderbilt-Ingram Cancer Center

Howard M Katzenstein
Ph: 800-811-8480

Texas
Austin

Dell Children's Medical Center of Central Texas

Amy C Fowler
Ph: 214-648-7097

Corpus Christi

Driscoll Children's Hospital

M. C Johnson
Ph: 361-694-5311

Dallas

Medical City Dallas Hospital

Carl Lenarsky
Ph: 972-566-5588

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Tamra L Slone
Ph: 214-648-7097

El Paso

El Paso Children's Hospital

Lisa L Hartman
Ph: 888-823-5923
Email: ctsucontact@westat.com

Fort Worth

Cook Children's Medical Center - Fort Worth

Mary Meaghan P Granger
Ph: 682-885-2103

Houston

Dan L. Duncan Cancer Center at Baylor College of Medicine

Karen R Rabin
Ph: 713-798-1354
Email: burton@bcm.edu

Univeristy of Texas M.D. Anderson Cancer Center

Robert J Wells
Ph: 713-792-3245

Lubbock

Covenant Children's Hospital

Latha Prasannan
Ph: 806-725-8000
Email: jaccresearch@covhs.org

San Antonio

Children's Hospital of San Antonio

Timothy C Griffin
Ph: 713-798-1354
Email: burton@bcm.edu

Methodist Children's Hospital of South Texas

Jaime Estrada
Ph: 210-575-7000

University of Texas Health Science Center at San Antonio

Anne-Marie R Langevin
Ph: 210-450-3800
Email: CTO@uthscsa.edu

Temple

Scott and White Cancer Institute

Guy H Grayson
Ph: 254-724-5407

Utah
Salt Lake City

Primary Children's Medical Center

Phillip E Barnette
Ph: 801-585-5270

Vermont
Burlington

University of Vermont Cancer Center

Alan C Homans
Ph: 802-656-4101

Virginia
Charlottesville

University of Virginia Cancer Center

Kimberly P Dunsmore
Ph: 434-243-6143

Falls Church

Inova Fairfax Hospital

Marshall A Schorin
Ph: 703-208-6650

Norfolk

Children's Hospital of The King's Daughters

Eric J Lowe
Ph: 757-668-7243

Portsmouth

Naval Medical Center - Portsmouth

Bethany M Mikles
Ph: 757-953-5939

Richmond

Virginia Commonwealth University Massey Cancer Center

Christina M Wiedl
Ph: 804-628-1939

Roanoke

Carilion Medical Center for Children at Roanoke Community Hospital

Mandy M Atkinson
Ph: 540-981-7376

Washington
Seattle

Children's Hospital and Regional Medical Center - Seattle

Douglas S Hawkins
Ph: 866-987-2000

Spokane

Providence Cancer Center at Sacred Heart Medical Center

Judy L Felgenhauer
Ph: 800-228-6618
Email: HopeBeginsHere@providence.org

Tacoma

Madigan Army Medical Center - Tacoma

Melissa A Forouhar
Ph: 253-968-0129
Email: mamcdci@amedd.army.mil

Mary Bridge Children's Hospital and Health Center - Tacoma

Robert G Irwin
Ph: 253-403-3229

West Virginia
Charleston

West Virginia University Medical School - Charleston

Howard M Grodman
Ph: 304-388-9944

Morgantown

Mary Babb Randolph Cancer Center at West Virginia University Hospitals

Stephan R Paul
Ph: 304-293-2745
Email: sfilburn@hsc.wvu.edu

Wisconsin
Green Bay

St. Vincent Hospital Regional Cancer Center

John R Hill
Ph: 920-433-8889

Madison

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Kenneth B DeSantes
Ph: 608-262-5223

Marshfield

Marshfield Clinic - Marshfield Center

Michael J McManus
Ph: 715-389-4457

Milwaukee

Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Richard L Tower
Ph: 414-805-4380

Australia

New South Wales
Hunter Regional Mail Centre

John Hunter Hospital

Elizabeth L Hesketh
Ph: 888-823-5923
Email: ctsucontact@westat.com

Queensland
Herston

Royal Brisbane and Women's Hospital

Helen Irving
Ph: 888-823-5923
Email: ctsucontact@westat.com

South Brisbane

Lady Cilento Children's Hospital

Helen Irving
Ph: 888-823-5923
Email: ctsucontact@westat.com

Victoria
Clayton

Monash Medical Center - Clayton Campus

Peter A Downie
Ph: 888-823-5923
Email: ctsucontact@westat.com

Parkville

Royal Children's Hospital

Francoise M Mechinaud
Email: crdo.info@mcri.edu.au

Western Australia
Perth

Princess Margaret Hospital for Children

Catherine H Cole
Ph: (08) 9340 8222
Email: catherine.cole@health.wa.gov.au

Canada

Alberta
Calgary

Alberta Children's Hospital

Douglas R Strother
Ph: 403-220-6898
Email: research4kids@ucalgary.ca

Edmonton

University of Alberta Hospital

Sunil Jayantilal S Desai
Ph: 780-407-6615
Email: val.taylor@albertahealthservices.ca

Manitoba
Winnipeg

CancerCare Manitoba

Rochelle A Yanofsky
Ph: 866-561-1026
Email: CIO_Web@cancercare.mb.ca

Newfoundland and Labrador
Saint John's

Janeway Children's Health and Rehabilitation Centre

Lisa Anne B Goodyear
Ph: 866-722-1126

Nova Scotia
Halifax

IWK Health Centre

Conrad V Fernandez
Ph: 902-470-8394

Ontario
Kingston

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Mariana P Silva
Ph: 613-544-2630

London

Children's Hospital of Western Ontario

Shayna M Zelcer
Ph: 519-685-8306

Ottawa

Children's Hospital of Eastern Ontario

Jacqueline M Halton
Ph: 613-738-3931

Toronto

Hospital for Sick Children

Sarah W Alexander
Ph: 416-813-7654ext2027
Email: jason.mcguire@sickkids.ca

Quebec
Montreal

Montreal Children's Hospital at McGill University Health Center

Sharon B Abish
Ph: 514-412-4445
Email: info@thechildren.com

Saskatchewan
Saskatoon

Saskatoon Cancer Centre at the University of Saskatchewan

Christopher Mpofu
Ph: 306-655-2914

Ireland

Co Dublin
Dublin

Our Lady's Hospital for Sick Children Crumlin

Michael L Capra
Ph: 353 1 4096419

New Zealand

Christchurch

Christchurch Hospital

Siobhan F Cross
Ph: 03 364 0640

Auckland
Grafton

Starship Children's Health

Lochie R Teague
Ph: 0800 728 436

Switzerland

Geneva

Swiss Pediatric Oncology Group Geneva

Marc Ansari
Ph: 031 389 91 89

Lausanne

Swiss Pediatric Oncology Group Lausanne

Maja Beck Popovic
Ph: 31 389 91 89

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01406756
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.