Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActiveUnder 30NCINCI-2011-02670
COG-AAML1031, CDR0000701850, AAML1031, U10CA180886, U10CA098543, NCT01371981

Trial Description

Summary

This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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 bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia.

Further Study Information

PRIMARY OBJECTIVES:

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

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

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

IV. To determine the feasibility of administering sorafenib (sorafenib tosylate) with standard chemotherapy and in a one year maintenance phase in patients with de novo high allelic ratio FLT3/ITD+ AML.

SECONDARY OBJECTIVES:

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

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

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

IV. To compare OS, DFS, cumulative incidence of relapse, treatment-related mortality, and severe toxicity between patients allocated to matched family donor SCT on AAML1031 and AAML0531.

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

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

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

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

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

X. To evaluate the prognostic significance of molecular MRD and its contribution to risk identification with multidimensional flow cytometry (MDF)-based MRD in patients with translocations amenable to quantitative real time (RT)-polymerase chain reaction (PCR) (e.g., t[8;21], inv[16], t[9;11], Wilms tumor 1 [WT1] expression).

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

XII. To define the leukemic stem cell population in patients with AML. XIII. To determine the prevalence and prognostic significance of molecular abnormalities of WT1, runt-related transcription factor (RUNX)1, mixed-lineage leukemia (MLL)-partial tandem duplication (PTD), tet methylcytosine dioxygenase 2 (TET2), Cbl proto-oncogene, E3 ubiquitin protein ligase (c-CBL), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and other novel AML-associated genes in pediatric AML.

XIV. Correlate the expression of cluster of differentiation (CD)74 antigen as well as proteasome beta 5-subunit (PSMB5) gene expression and mutation with response to bortezomib.

XV. To evaluate the changes in protein expression and unfolded protein response (UPR) in patients with AML.

XVI. To determine the expression level of wild-type FLT3, and correlate with outcome and in vitro sensitivity to FLT3 inhibition.

XVII. To collect biology specimens at diagnosis, treatment time points, and relapse for future biology studies XVIII. To create a pediatric-specific algorithm to predict the occurrence of grade 2-4 acute graft-versus-host disease (GVHD) prior to its clinical manifestations using a combination of pre-transplant clinical variables and serum GVHD biomarker concentrations in the first weeks after SCT.

OUTLINE: This is a dose-escalation study of sorafenib tosylate. Patients are randomized to 1 of 2 treatment arms or offered treatment on a third arm.

INDUCTION I:

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

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

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

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

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

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

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

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

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

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

INTENSIFICATION I:

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

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

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

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

INTENSIFICATION II:

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

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

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

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

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

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

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

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

MAINTENANCE: Patients in Arm C receive sorafenib tosylate PO starting on day 40-80 after completion of intensification II or SCT for one year.

After completion of study therapy, patients are followed up monthly for 6 months, every 2 months for 6 months, every 4 months for 1 year, every 6 months for 1 year, and then yearly thereafter.

Eligibility Criteria

Inclusion Criteria:

  • Patients must be newly diagnosed with de novo acute myelogenous leukemia
  • Patients with previously untreated primary AML who meet the customary criteria for AML with >= 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible
  • Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/fluorescent in situ hybridization (FISH) testing is feasible can be substituted for the marrow exam at diagnosis
  • Patients with < 20% bone marrow blasts are eligible if they have:
  • A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities)
  • The unequivocal presence of megakaryoblasts, or
  • Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
  • Patients with any performance status are eligible for enrollment
  • Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed
  • Hydroxyurea and ATRA must be discontinued prior to initiation of protocol therapy
  • Patients who have previously received any other chemotherapy, radiation therapy or any other antileukemic therapy are not eligible for this protocol
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with any of the following constitutional conditions are not eligible:
  • Fanconi anemia
  • Shwachman syndrome
  • Any other known bone marrow failure syndrome
  • Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Note: Enrollment may occur pending results of clinically indicated studies to exclude these conditions
  • Patients with any of the following oncologic diagnoses are not eligible:
  • Any concurrent malignancy
  • Juvenile myelomonocytic leukemia (JMML)
  • Philadelphia chromosome positive AML
  • Biphenotypic or bilineal acute leukemia
  • Acute promyelocytic leukemia
  • Acute myeloid leukemia arising from myelodysplasia
  • Therapy-related myeloid neoplasms Note: Enrollment may occur pending results of clinically indicated studies to exclude these conditions
  • Pregnancy and breast feeding
  • Female patients who are pregnant are ineligible
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • 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

National Cancer Institute

    Richard Aplenc, 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

    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

    Yi Zeng
    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

    Theresa M Harned
    Ph: 800-826-4673
    Email: becomingapatient@coh.org

    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

    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 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

    Mark J Mogul
    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

    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

    Nobuko Hijiya
    Ph: 773-880-4562

    University of Chicago Cancer Research Center

    Jennifer L McNeer
    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

    Jong-Hyo Kwon
    Ph: 847-384-3621

    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
    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

    Bethesda

    National Naval Medical Center

    Anne B Warwick
    Ph: 301-319-2100

    Massachusetts
    Boston

    Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

    Carlos Rodriguez-Galindo
    Ph: 866-790-4500

    Floating Hospital for Children at Tufts - New England Medical Center

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

    Massachusetts General Hospital

    Howard J Weinstein
    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

    Rajen Mody
    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

    Jeffrey W Taub
    Ph: 313-576-9363

    East Lansing

    Breslin Cancer Center at Ingham Regional Medical Center

    Renuka Gera
    Ph: 517-975-9547

    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

    Carola A. S. Arndt
    Ph: 507-538-7623

    Mississippi
    Jackson

    University of Mississippi Cancer Clinic

    Gail C Megason
    Ph: 601-815-6700

    Missouri
    Columbia

    Columbia Regional Hospital

    Thomas W Loew
    Ph: 573-882-7440

    Saint Louis

    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

    Cancer Institute of Nevada at Summerlin Hospital Medical Center

    Jonathan Bernstein
    Ph: 702-384-0013

    CCOP - Nevada Cancer Research Foundation

    Jonathan Bernstein
    Ph: 702-384-0013

    Children's Specialty Center of 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

    Richard Aplenc
    Ph: 240-276-6515

    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

    Buffalo

    Roswell Park Cancer Institute

    Lynda K Beaupin
    Ph: 877-275-7724

    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

    Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    Alice Lee
    Ph: 212-305-8615

    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

    Durham

    Duke Cancer Institute

    Susan G Kreissman
    Ph: 888-275-3853

    Winston-Salem

    Wake Forest University Comprehensive Cancer Center

    Sharon M Castellino
    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

    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

    Legacy Emanuel Hospital and Health Center and 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

    Richard Aplenc
    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

    Rakesh K Goyal
    Ph: 412-692-5573

    PR
    San Juan

    San Jorge Children's Hospital

    Luis A Clavell
    Ph: 888-823-5923
    Email: ctsucontact@westat.com

    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

    Venita L Williams
    Ph: 714-734-6220

    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

    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

    Kenneth M Heym
    Ph: 682-885-2103

    Houston

    Dan L. Duncan Cancer Center at Baylor College of Medicine

    Michele S Redell
    Ph: 713-798-1354
    Email: burton@bcm.edu

    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
    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

    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

    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

    Draga Barbaric
    Ph: (02) 9382-1721

    Randwick

    Sydney Children's Hospital

    Draga Barbaric
    Ph: (02) 9382-1721

    Westmead

    Children's Hospital at Westmead

    Geoffrey B McCowage
    Ph: 61-2-9845 1400

    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
    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

    British Columbia
    Vancouver

    Children's and Women's Hospital of British Columbia

    Caron Strahlendorf
    Ph: 604-875-2345ext6477

    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
    Hamilton

    McMaster Children's Hospital at Hamilton Health Sciences

    Carol Portwine
    Ph: 905-521-2100ext74595

    Carol Portwine
    Ph: 905-521-2100ext74595

    Kingston

    Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Mariana P Silva
    Ph: 613-544-2630

    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

    Hopital Sainte Justine

    Yvan Samson
    Ph: 514-345-4931

    Montreal Children's Hospital at McGill University Health Center

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

    Quebec

    Centre de Recherche du Centre Hospitalier de l'Universite Laval

    Bruno Michon
    Ph: 418-525-4444

    New Zealand

    Christchurch

    Christchurch Hospital

    Nyree O Cole
    Ph: 0800 728 436

    Auckland
    Grafton

    Starship Children's Health

    Lochie R Teague
    Ph: 0800 728 436

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT01371981
    ClinicalTrials.gov processed this data on May 18, 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.