Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase II/III trial is studying how well giving bortezomib and sorafenib tosylate together works in treating patients with newly diagnosed acute myeloid leukemia with or without mutations. 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 more than one drug (combination chemotherapy) may kill more cancer cells. 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) of patients with de novo acute myeloid leukemia (AML) with or without high allelic ratio FLT3/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 COG-AAML0531.

IV. To determine the feasibility of combining sorafenib with standard chemotherapy in patients with de novo high allelic ratio FLT3/ITD+ AML.

SECONDRY 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 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 COG-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 AAML103P1 and AAML0531.

V. To assess the health-related quality of life (HRQOL) of patients treated with chemotherapy and 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 RT-PCR (e.g., t(8;21), inv(16), t(9;11), 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, RUNX1, MLL-PTD, TET2, c-CBL, KIT, and other novel AML-associated genes in pediatric AML.

XIV. To correlate the expression of CD74 antigen as well as 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.

OUTLINE: This is a multicenter, dose-escalation study of sorafenib tosylate and an open-label randomized study. Patients are stratified according to disease risk (low vs high). 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 IV over 15-30 minutes on days 1-10; daunorubicin 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 15-30 minutes on days 1-8, daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and 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 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.

GRAFT-VS-HOST DISEASE (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.

Blood, bone marrow, and tissue samples are collected at baseline and periodically during study for mutation and translocation analysis, cytogenetic/FISH analysis, gene and protein expression, and other studies. Some patients (aged 2 to 18 years) and/or parents may complete questionnaires about health-related quality of life (Pediatric Quality of Life (PedsQL) 4.0 Generic Core Scale, the PedsQL 3.0 Acute Cancer Module, and the PedsQL Multidimensional Fatigue Scale) and parental stress (Pediatric Inventory for Parents (PIP) scale) at baseline and periodically during the study and follow-up.

After completion of study therapy, patients are followed up monthly for 6 months, every 2 months for 6 months, every 3 months for 1 year, every 6 months for 1 year, and then yearly for up to 8 years.

Eligibility Criteria

Inclusion Criteria:

• Patients must be newly diagnosed with de novo acute myelogenous leukemia and must meet 1 of the following criteria:

• Patients with previously untreated primary AML who meet the customary criteria for AML with ≥ 20% bone marrow blasts as set out in the 2008 WHO Myeloid Neoplasm Classification are eligible

• Patients with cytopenias and bone marrow blasts who do not meet the customary criteria for the diagnosisof AML (patients with < 20% blasts) are eligible if they have a karyotypic abnormality characteristic ofde novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities), or ifthey have the unequivocal presence of megakaryoblasts, as set out in the 2008 WHO Myeloid NeoplasmClassification

• Patients with biopsy-proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemiacutis) are eligible

• Patients must meet one of the following criteria:

• Low-risk disease as defined by any of the following:

• Presence of [inv(16)/t(16;16) or t(8;21)] or presence of NPM orCEBPα mutation, regardless of minimum-residual disease (MRD) status at end of Induction I

• Standard-risk cytogenetics (neitherfavorable or unfavorable) with negative MRD (< 0.1%) at end of Induction I

• Patients who do not have MRD data and have non-informative molecular studies (NPM, CEBPα,and cytogenetics) will be classified as having low-risk disease

• High-risk disease as defined by any of the following:

• FLT3/ITD+ with high allelic ratio (HR FLT3/ITD+)

• Unfavorablecytogenetics (monosomy 7, monosomy 5, and del5q)

• Standard-risk cytogenetics with positive MRD(≥ 0.1%) at end of Induction I

• Patients with juvenile myelomonocytic leukemia (JMML) are not eligible

• Patients with Philadelphia chromosome positive AML, biphenotypic or bilineal acute leukemia,or acute promyelocytic leukemia are not eligible

• High-risk patients may have a donor (bone marrow or cord blood) meeting the following criteria available:

• Matched family donor (MFD)*

• HLA, A, B, C, DRB1, identical, or 1 antigen or allele mismatched

• HLA typing must be performed using molecular high-resolution technique

• All available first-degree family members (parents and siblings) must be HLA typed

• Use of syngeneic donors will NOT be permitted in this study

• Alternative donor

• HLA, A, B, C, DRB1 identical or 1 antigen- or allele-mismatched unrelated donor

• HLA A, B, DRB1 4 of 6 antigen-matched unrelated donor cord blood unit with an adequatecell dose (nucleated cell dose > 3.7x10^7/kg or CD34+ cell dose > 2 x 10^5/kg)

• Mismatched family member donor with at least one haplotype match, or 5 of 6 antigenphenotypic match

• Patients with any performance status are eligible

• Patients with constitutional trisomy 21 are not eligible

• Patients with any of the following are not eligible:

• Fanconi anemia

• Shwachman syndrome

• Any other known bone marrow failure syndrome

• Another concurrent malignancy

• Not pregnant or nursing

• Negative pregnancy test

• Sexually active patients of reproductive potential are not eligible unless they have agreed to use aneffective contraceptive method for the duration of their study participation

• Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and intrathecal (IT) cytarabinegiven at diagnosis is allowed

• Hydroxyurea and ATRA must be discontinued prior to initiation of protocoltherapy

• No concurrent peripheral blood stem cell transplantation

• Patients who have previously received any other chemotherapy, radiation therapy, or any otherantileukemic therapy are not eligible for this protocol

• Concomitant administration of strong CYP3A4 inducers and inhibitors (including clinicallyrelevant moderate inhibitors) is prohibited on both sorafenib cohorts

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Richard Aplenc

Principal Investigator

U.S.A.
Alabama
	Birmingham
	Children's Hospital of Alabama at University of Alabama at Birmingham
		Alyssa T Reddy	Ph: 205-934-0309
	UAB Comprehensive Cancer Center
		Alyssa T Reddy	Ph: 205-934-0309
	Mobile
	University of South Alabama Mitchell Cancer Institute
		Felicia L Wilson	Ph: 251-665-8000
Arizona
	Phoenix
	Phoenix Children's Hospital
		Jessica Boklan	Ph: 602-546-0920
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		David L Becton	Ph: 501-364-7373
California
	Arcadia
	Children's Oncology Group
		Richard Aplenc
			Email: aplenc@email.chop.edu
	Downey
	Southern California Permanente Medical Group
		Robert M Cooper	Ph: 626-564-3455
	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
		Shadi Farzin-Gohar	Ph: 909-558-3375
	Los Angeles
	Childrens 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
		Vincent A Kiley	Ph: 626-564-3455
	Orange
	Children's Hospital of Orange County
		Violet Shen	Ph: 714-997-3000
	Sacramento
	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
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
		Christopher N Frantz	Ph: 302-651-5755
Florida
	Fort Lauderdale
	Broward General Medical Center Cancer Center
		Hector M Rodriguez-Cortes	Ph: 954-355-5346
	Fort Myers
	Lee Cancer Care of Lee Memorial Health System
		Emad K Salman	Ph: 239-343-5333
	Gainesville
	University of Florida Shands 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
		Eric S Sandler	Ph: 904-697-3529
	Miami
	Baptist-South Miami Regional Cancer Program
		Doured Daghistani	Ph: 800-599-2456
			Email: cancerinfo@baptisthealth.net
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		Julio C Barredo	Ph: 866-574-5124
			Email: Sylvester@emergingmed.com
	Orlando
	Florida Hospital Cancer Institute at Florida Hospital Orlando
		Clifford A Selsky	Ph: 407-303-5623
	M.D. Anderson Cancer Center at Orlando
		Vincent F Giusti	Ph: 321-841-7246
	Nemours Children's Clinic - Orlando
		Ramamoorthy Nagasubramanian	Ph: 407-650-7150
	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
		Hardeo K Panchoosingh	Ph: 800-882-4123
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Howard M Katzenstein	Ph: 888-785-1112
	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. Martin Johnston	Ph: 912-350-8568
Hawaii
	Honolulu
	Cancer Research Center of Hawaii
		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
		David O Walterhouse	Ph: 773-880-4562
	University of Illinois Cancer Center
		Mary L Schmidt	Ph: 312-355-3046
	Maywood
	Cardinal Bernardin Cancer Center at Loyola University Medical Center
		Ricarchito B Manera	Ph: 708-226-4357
	Oak Lawn
	Keyser Family Cancer Center at Advocate Hope Children's Hospital
		Sharad N Salvi	Ph: 847-723-7570
	Park Ridge
	Advocate Lutheran General Cancer Care Center
		Jong H 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: 888-823-5923
			Email: ctsucontact@westat.com
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Raymond Tannous	Ph: 800-237-1225
Kentucky
	Lexington
	University of Kentucky Chandler Medical Center
		Martha F Greenwood	Ph: 859-257-3379
	Louisville
	Kosair Children's Hospital
		Salvatore J Bertolone	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
		Rajasekharan P. Warrier	Ph: 504-894-5377
	Tulane Cancer Center at Tulane University Hospital and Clinic
		Tammuella C Singleton	Ph: 504-988-6121
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
		Johannes E Wolff	Ph: 617-636-5000
			Email: ContactUsCancerCenter@TuftsMedicalCenter.org
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
	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
	Lansing
	Breslin Cancer Center at Ingham Regional Medical Center
		Renuka Gera	Ph: 517-334-2765
Minnesota
	Minneapolis
	Children's Hospitals and Clinics of Minnesota - Minneapolis
		Bruce C Bostrom	Ph: 612-813-5193
	Masonic Cancer Center at University of Minnesota
		Michael J Burke	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
	Kansas City
	Children's Mercy Hospital
		Maxine L Hetherington	Ph: 816-234-3265
	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
	UNMC Eppley Cancer Center at the University of Nebraska Medical Center
		Peter F Coccia	Ph: 800-999-5465
Nevada
	Las Vegas
	CCOP - Nevada Cancer Research Foundation
		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
	Livingston
	St. Barnabas Medical Center Cancer Center
		Stacey Rifkin-Zenenberg	Ph: 973-926-7230
	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
New York
	Albany
	Albany Medical Center Hospital
		Vikramjit S Kanwar	Ph: 518-262-3368
	Bronx
	Montefiore Medical Center
		Rosanna J Ricafort	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
		Elizabeth A Raetz	Ph: 212-263-4434
			Email: prmc.coordinator@nyumc.org
	Rochester
	James P. Wilmot Cancer Center at University of Rochester Medical Center
		Lisa R Hackney	Ph: 585-275-5830
	Syracuse
	SUNY Upstate Medical University Hospital
		Karol H Kerr	Ph: 315-464-5476
	Valhalla
	New York Medical College
		Mehmet F Ozkaynak	Ph: 914-594-3794
North Carolina
	Asheville
	Mission Hospitals - Memorial Campus
		Orren Beaty	Ph: 828-213-4150
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Stuart H Gold	Ph: 877-668-0683
	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
	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
		Nathan L Kobrinsky	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
		Tanya M Tekautz	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
		Dagmar T Stein	Ph: 419-824-1842
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		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
		Jeffrey S Taylor	Ph: 570-271-5251
	Hershey
	Penn State Children's Hospital
		Lisa M McGregor	Ph: 717-531-6012
	Philadelphia
	Children's Hospital of Philadelphia
		Frank M Balis	Ph: 215-590-2810
	Pittsburgh
	Children's Hospital of Pittsburgh of UPMC
		Arthur K Ritchey	Ph: 412-692-5573
PR
	Santurce
	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
		Cindy L Schwartz	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
South Dakota
	Sioux Falls
	Sanford Cancer Center at Sanford USD Medical Center
		Kayelyn J Wagner	Ph: 605-328-1367
Tennessee
	Knoxville
	East Tennessee Children's Hospital
		Ray C Pais	Ph: 865-541-8266
	Nashville
	Vanderbilt-Ingram Cancer Center
		Haydar A Frangoul	Ph: 800-811-8480
Texas
	Austin
	Dell Children's Medical Center of Central Texas
		Sharon K Lockhart	Ph: 512-324-8022
	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
		Naomi J Winick	Ph: 214-648-7097
	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
	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: 210-567-0653
			Email: che@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
	Vermont Cancer Center at University of Vermont
		Alan C Homans	Ph: 802-656-8990
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
		Kamar Godder	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
		Jessica A Pollard	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
	Mary Bridge Children's Hospital and Health Center - Tacoma
		Robert G Irwin	Ph: 888-823-5923
			Email: ctsucontact@westat.com
West Virginia
	Charleston
	West Virginia University Medical School - Charleston
		Allen R Chauvenet	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 De Santes	Ph: 608-262-5223
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Richard L Tower	Ph: 414-805-4380
Australia
New South Wales
	Randwick
	Sydney Children's Hospital
		Draga Barbaric	Ph: (02) 9382-1721
	Sydney
	Children's Hospital at Westmead
		Luciano Dalla-Pozza	Ph: 61-2-9845 1400
Queensland
	Herston
	Royal Brisbane and Women's Hospital
		Helen Irving	Ph: 888-823-5923
			Email: ctsucontact@westat.com
	Royal 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 8330
			Email: admin@childcancerresearch.com.au
Canada
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
		Margaret C Yhap	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
		Ronald M Grant	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
	Ste-Foy
	Centre de Recherche du Centre Hospitalier de l'Universite Laval
		Bruno Michon	Ph: 418-525-4444
New Zealand
	Christchurch
	Christchurch Hospital
		Michael J Sullivan	Ph:  03 364 0640
Auckland
	Grafton
	Starship Children's Health
		Lochie R Teague	Ph:  0800 728 436

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01371981
Information obtained from ClinicalTrials.gov on March 04, 2013