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

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActiveUnder 30AAML1031
NCI-2011-02670, COG-AAML1031, CDR0000701850, 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 1 of 2 arms. (Arms A and B are closed to new patient enrollment as of 02/04/2016)

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 over 3-5 seconds 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.

ARM D (unknown FLT3/ITD status prior to study enrollment): Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. If patients are determined to be HR FLT3/ITD+ no later than the end of Induction I they will be eligible to participate in Arm C.

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, cohort 3): 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 9-36.

Patients who achieve complete remission (CR) proceed to Intensification I (beginning on day 37). 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 (cohort 3): Patients receive cytarabine IT and AE chemotherapy in Intensification II, Arm A, and sorafenib tosylate PO on daily on days 6-28.

Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 34. 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 cohort 3): Patients receive cytarabine IT on day 1, MA chemotherapy as in Induction II, Arm A (HR patients), and sorafenib tosylate PO on days 7-34.

STEM CELL TRANSPLANTATION (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 40-100 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

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 / Collaborators

National Cancer Institute

  • National Cancer Institute
Richard Aplenc, Principal Investigator

Trial Sites

U.S.A.

Alabama
Birmingham

Children's Hospital of Alabama

Alyssa Terry Reddy
Ph: 205-638-9285

Alyssa Terry Reddy
Principal Investigator

Mobile

University of South Alabama

Felicia Little Wilson
Ph: 251-665-8000

Felicia Little Wilson
Principal Investigator

Arizona
Mesa

Cardon Children's Medical Center

Xiaxin Li
Ph: 602-747-9738

Xiaxin Li
Principal Investigator

Phoenix

Phoenix Childrens Hospital

Jessica Boklan
Ph: 602-546-0920

Jessica Boklan
Principal Investigator

Tucson

The University of Arizona Medical Center-University Campus

Yi Zeng
Ph: 520-626-9008

Yi Zeng
Principal Investigator

Arkansas
Little Rock

Arkansas Children's Hospital

David L. Becton
Ph: 501-364-7373

David L. Becton
Principal Investigator

California
Downey

Southern California Permanente Medical Group

Robert Michael Cooper
Ph: 626-564-3455

Robert Michael Cooper
Principal Investigator

Loma Linda

Loma Linda University Medical Center

Albert Kheradpour
Ph: 909-558-3375

Albert Kheradpour
Principal Investigator

Long Beach

Miller Children's and Women's Hospital Long Beach

Pamela Helen-Heilge Kempert
Ph: 562-933-5600

Pamela Helen-Heilge Kempert
Principal Investigator

Los Angeles

Children's Hospital Los Angeles

Leo Mascarenhas
Ph: 323-361-4110

Leo Mascarenhas
Principal Investigator

Madera

Children's Hospital Central California

Vonda Lee Crouse
Ph: 866-353-5437

Vonda Lee Crouse
Principal Investigator

Oakland

Children's Hospital and Research Center at Oakland

Carla Barbara Golden
Ph: 510-450-7600

Carla Barbara Golden
Principal Investigator

Kaiser Permanente-Oakland

Steven K. Bergstrom
Ph: 626-564-3455

Steven K. Bergstrom
Principal Investigator

Orange

Children's Hospital of Orange County

Violet Shen
Ph: 714-997-3000

Violet Shen
Principal Investigator

Sacramento

Sutter General Hospital

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

Yung Soon Yim
Principal Investigator

University of California Davis Comprehensive Cancer Center

Marcio Henrique Malogolowkin
Ph: 916-734-3089

Marcio Henrique Malogolowkin
Principal Investigator

San Francisco

UCSF Medical Center-Mission Bay

Mignon Lee-Cheun Loh
Ph: 877-827-3222

Mignon Lee-Cheun Loh
Principal Investigator

Santa Barbara

Santa Barbara Cottage Hospital

Daniel J. Greenfield
Ph: 805-682-7300

Daniel J. Greenfield
Principal Investigator

Colorado
Aurora

Children's Hospital Colorado

Kelly Wilson Maloney
Ph: 720-777-6672

Kelly Wilson Maloney
Principal Investigator

Denver

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Jennifer Jocelyn Clark
Ph: 866-775-6246

Jennifer Jocelyn Clark
Principal Investigator

Connecticut
Hartford

Connecticut Children's Medical Center

Michael Scott Isakoff
Ph: 860-545-9981

Michael Scott Isakoff
Principal Investigator

New Haven

Yale University

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

Nina Singh Kadan-Lottick
Principal Investigator

Delaware
Wilmington

Alfred I duPont Hospital for Children

Jeffrey H. Schwartz
Ph: 904-697-3529

Jeffrey H. Schwartz
Principal Investigator

District of Columbia
Washington

Children's National Medical Center

Jeffrey Stuart Dome
Ph: 202-884-2549

Jeffrey Stuart Dome
Principal Investigator

Florida
Fort Lauderdale

Broward Health Medical Center

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

Hector M. Rodriguez-Cortes
Principal Investigator

Fort Myers

Golisano Children's Hospital of Southwest Florida

Emad K. Salman
Ph: 239-343-5333

Emad K. Salman
Principal Investigator

Gainesville

University of Florida

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

William Birdsall Slayton
Principal Investigator

Hollywood

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Iftikhar Hanif
Ph: 954-265-2234

Iftikhar Hanif
Principal Investigator

Jacksonville

Nemours Children's Clinic-Jacksonville

Jeffrey H. Schwartz
Ph: 904-697-3529

Jeffrey H. Schwartz
Principal Investigator

Miami

Baptist Hospital of Miami

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

Doured Daghistani
Principal Investigator

Nicklaus Children's Hospital

Enrique Alberto Escalon
Ph: 888-624-2778

Enrique Alberto Escalon
Principal Investigator

University of Miami Miller School of Medicine-Sylvester Cancer Center

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

Julio Cesar Barredo
Principal Investigator

Orlando

Arnold Palmer Hospital for Children

Vincent Ferdinando Giusti
Ph: 321-843-2584

Vincent Ferdinando Giusti
Principal Investigator

Florida Hospital Orlando

Fouad M. Hajjar
Ph: 407-303-2090
Email: FH.Cancer.Research@flhosp.org

Fouad M. Hajjar
Principal Investigator

Saint Petersburg

Johns Hopkins All Children's Hospital

Gregory Alan Hale
Ph: 727-767-4784
Email: Ashley.Repp@jhmi.edu

Gregory Alan Hale
Principal Investigator

Tampa

Saint Joseph's Hospital/Children's Hospital-Tampa

Mark J. Mogul
Ph: 800-882-4123

Mark J. Mogul
Principal Investigator

Tampa General Hospital

Cameron K. Tebbi
Ph: 800-882-4123
Email: hkourtellis@tgh.org

Cameron K. Tebbi
Principal Investigator

West Palm Beach

Saint Mary's Hospital

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

Narayana Gowda
Principal Investigator

Georgia
Atlanta

Children's Healthcare of Atlanta - Egleston

Glen Lew
Ph: 404-785-1112

Glen Lew
Principal Investigator

Savannah

Memorial University Medical Center

J. Martin Johnston
Ph: 912-350-8568

J. Martin Johnston
Principal Investigator

Hawaii
Honolulu

Kapiolani Medical Center for Women and Children

Wade T. Kyono
Ph: 808-983-6090

Wade T. Kyono
Principal Investigator

Idaho
Boise

Saint Luke's Mountain States Tumor Institute

Eugenia Chang
Ph: 208-381-3376
Email: mcdonagd@slhs.org

Eugenia Chang
Principal Investigator

Illinois
Chicago

Lurie Children's Hospital-Chicago

Nobuko Hijiya
Ph: 773-880-4562

Nobuko Hijiya
Principal Investigator

University of Chicago Comprehensive Cancer Center

Jennifer Lynn McNeer
Ph: 773-834-7424

Jennifer Lynn McNeer
Principal Investigator

University of Illinois

Mary Lou Schmidt
Ph: 312-355-3046

Mary Lou Schmidt
Principal Investigator

Maywood

Loyola University Medical Center

Eugene Suh
Ph: 708-226-4357

Eugene Suh
Principal Investigator

Oak Lawn

Advocate Children's Hospital-Oak Lawn

Rebecca Erin McFall
Ph: 847-723-7570

Rebecca Erin McFall
Principal Investigator

Park Ridge

Advocate Children's Hospital-Park Ridge

Jong-Hyo Kwon
Ph: 847-384-3621

Jong-Hyo Kwon
Principal Investigator

Springfield

Southern Illinois University School of Medicine

Gregory P. Brandt
Ph: 217-545-7929

Gregory P. Brandt
Principal Investigator

Indiana
Indianapolis

Riley Hospital for Children

Robert J. Fallon
Ph: 800-248-1199

Robert J. Fallon
Principal Investigator

Saint Vincent Hospital and Health Care Center

Bassem I. Razzouk
Ph: 317-338-2194
Email: research@stvincent.org

Bassem I. Razzouk
Principal Investigator

Iowa
Des Moines

Blank Children's Hospital

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

Wendy Leigh Woods-Swafford
Principal Investigator

Iowa City

University of Iowa/Holden Comprehensive Cancer Center

Mariko Sato
Ph: 800-237-1225

Mariko Sato
Principal Investigator

Kentucky
Lexington

University of Kentucky/Markey Cancer Center

Lars Martin Wagner
Ph: 859-257-3379

Lars Martin Wagner
Principal Investigator

Louisville

Kosair Children's Hospital

Kenneth G. Lucas
Ph: 866-530-5516

Kenneth G. Lucas
Principal Investigator

Louisiana
New Orleans

Ochsner Medical Center Jefferson

Craig Lotterman
Ph: 888-562-4763

Craig Lotterman
Principal Investigator

Maine
Scarborough

Maine Children's Cancer Program

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

Eric C. Larsen
Principal Investigator

Maryland
Baltimore

Johns Hopkins University/Sidney Kimmel Cancer Center

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

Patrick A. Brown
Principal Investigator

Sinai Hospital of Baltimore

Jason M. Fixler
Ph: 410-601-6120
Email: pridgely@lifebridgehealth.org

Jason M. Fixler
Principal Investigator

University of Maryland/Greenebaum Cancer Center

Teresa Anne York
Ph: 800-888-8823

Teresa Anne York
Principal Investigator

Bethesda

Walter Reed National Military Medical Center

Anne Benedicta Warwick
Ph: 301-319-2100

Anne Benedicta Warwick
Principal Investigator

Massachusetts
Boston

Floating Hospital for Children at Tufts Medical Center

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

Michael J. Kelly
Principal Investigator

Worcester

University of Massachusetts Medical School

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

Christopher P. Keuker
Principal Investigator

Michigan
Ann Arbor

C S Mott Children's Hospital

Rajen Mody
Ph: 800-865-1125

Rajen Mody
Principal Investigator

Detroit

Saint John Hospital and Medical Center

Hadi Sawaf
Ph: 313-343-3166

Hadi Sawaf
Principal Investigator

East Lansing

Michigan State University Clinical Center

Renuka Gera
Ph: 517-975-9547

Renuka Gera
Principal Investigator

Grand Rapids

Helen DeVos Children's Hospital at Spectrum Health

David Scott Dickens
Ph: 616-391-1230
Email: crcwm-regulatory@crcwm.org

David Scott Dickens
Principal Investigator

Kalamazoo

Bronson Methodist Hospital

Katharina Elisabeth Elliott
Ph: 616-391-1230
Email: crcwm-regulatory@crcwm.org

Katharina Elisabeth Elliott
Principal Investigator

Royal Oak

Beaumont Children's Hospital-Royal Oak

Laura Kate Gowans
Ph: 248-551-7695

Laura Kate Gowans
Principal Investigator

Minnesota
Minneapolis

Children's Hospitals and Clinics of Minnesota - Minneapolis

Michael Kerr Richards
Ph: 612-813-5193

Michael Kerr Richards
Principal Investigator

University of Minnesota/Masonic Cancer Center

Peter Michael Gordon
Ph: 612-624-2620

Peter Michael Gordon
Principal Investigator

Rochester

Mayo Clinic

Carola A. S. Arndt
Ph: 855-776-0015

Carola A. S. Arndt
Principal Investigator

Mississippi
Jackson

University of Mississippi Medical Center

Gail Cranshaw Megason
Ph: 601-815-6700

Gail Cranshaw Megason
Principal Investigator

Missouri
Kansas City

The Childrens Mercy Hospital

Maxine Lorraine Hetherington
Ph: 816-234-3265

Maxine Lorraine Hetherington
Principal Investigator

Saint Louis

Mercy Hospital Saint Louis

Bethany Graham Sleckman
Ph: 913-948-5588

Bethany Graham Sleckman
Principal Investigator

Washington University School of Medicine

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

Robert J. Hayashi
Principal Investigator

Nebraska
Omaha

Children's Hospital and Medical Center of Omaha

Don Wilson Coulter
Ph: 402-559-6941
Email: unmcrsa@unmc.edu

Don Wilson Coulter
Principal Investigator

University of Nebraska Medical Center

Don Wilson Coulter
Ph: 402-559-6941
Email: unmcrsa@unmc.edu

Don Wilson Coulter
Principal Investigator

Nevada
Las Vegas

Nevada Cancer Research Foundation CCOP

Jonathan Bernstein
Ph: 702-384-0013

Jonathan Bernstein
Principal Investigator

New Hampshire
Lebanon

Dartmouth Hitchcock Medical Center

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

Sara Chaffee
Principal Investigator

New Jersey
Hackensack

Hackensack University Medical Center

Burton Eliot Appel
Ph: 201-996-2879

Burton Eliot Appel
Principal Investigator

Morristown

Morristown Medical Center

Steven Lon Halpern
Ph: 973-971-5900

Steven Lon Halpern
Principal Investigator

New Brunswick

Saint Peter's University Hospital

Nibal Ahmad Zaghloul
Ph: 732-745-8600extn6163
Email: kcovert@saintpetersuh.com

Nibal Ahmad Zaghloul
Principal Investigator

Newark

Newark Beth Israel Medical Center

Peri Kamalakar
Ph: 973-926-7230

Peri Kamalakar
Principal Investigator

Paterson

Saint Joseph's Regional Medical Center

Mary Ann Bonilla
Ph: 973-754-2909

Mary Ann Bonilla
Principal Investigator

New Mexico
Albuquerque

University of New Mexico Cancer Center

Koh B. Boayue
Ph: 505-272-6972

Koh B. Boayue
Principal Investigator

New York
Albany

Albany Medical Center

Vikramjit Singh Kanwar
Ph: 518-262-3368

Vikramjit Singh Kanwar
Principal Investigator

Buffalo

Roswell Park Cancer Institute

Lynda Kwon Beaupin
Ph: 877-275-7724

Lynda Kwon Beaupin
Principal Investigator

Mineola

Winthrop University Hospital

Mark E. Weinblatt
Ph: 866-946-8476

Mark E. Weinblatt
Principal Investigator

New Hyde Park

The Steven and Alexandra Cohen Children's Medical Center of New York

Arlene Sara Redner
Ph: 718-470-3470

Arlene Sara Redner
Principal Investigator

New York

Columbia University/Herbert Irving Cancer Center

Alice Lee
Ph: 212-305-8615

Alice Lee
Principal Investigator

Laura and Isaac Perlmutter Cancer Center at NYU Langone

Teena Bhatla
Ph: 212-263-4434
Email: prmc.coordinator@nyumc.org

Teena Bhatla
Principal Investigator

Weill Medical College of Cornell University

Alexander Aledo
Ph: 212-746-1848

Alexander Aledo
Principal Investigator

Rochester

University of Rochester

Jeffrey Robert Andolina
Ph: 585-275-5830

Jeffrey Robert Andolina
Principal Investigator

Stony Brook

Stony Brook University Medical Center

Robert Ingalls Parker
Ph: 800-862-2215

Robert Ingalls Parker
Principal Investigator

Syracuse

State University of New York Upstate Medical University

Melanie A. Comito
Ph: 315-464-5476

Melanie A. Comito
Principal Investigator

Valhalla

New York Medical College

Jessica Cassara Hochberg
Ph: 914-594-3794

Jessica Cassara Hochberg
Principal Investigator

North Carolina
Asheville

Mission Hospital-Memorial Campus

Douglas James Scothorn
Ph: 828-213-4150

Douglas James Scothorn
Principal Investigator

Chapel Hill

UNC Lineberger Comprehensive Cancer Center

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

Stuart Harrison Gold
Principal Investigator

Charlotte

Carolinas Medical Center/Levine Cancer Institute

Joel A. Kaplan
Ph: 704-355-2884

Joel A. Kaplan
Principal Investigator

Durham

Duke University Medical Center

Susan G. Kreissman
Ph: 888-275-3853

Susan G. Kreissman
Principal Investigator

Winston-Salem

Wake Forest University Health Sciences

Thomas Bennett Russell
Ph: 336-713-6771

Thomas Bennett Russell
Principal Investigator

North Dakota
Fargo

Sanford Medical Center-Fargo

Samuel Odame Anim
Ph: 701-234-6161

Samuel Odame Anim
Principal Investigator

Ohio
Cincinnati

Cincinnati Children's Hospital Medical Center

John Peter Perentesis
Ph: 513-636-2799

John Peter Perentesis
Principal Investigator

Cleveland

Cleveland Clinic Foundation

Aron Flagg
Ph: 866-223-8100

Aron Flagg
Principal Investigator

Rainbow Babies and Childrens Hospital

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

Yousif (Joe) H. Matloub
Principal Investigator

Columbus

Nationwide Children's Hospital

Mark Anthony Ranalli
Ph: 614-722-2708

Mark Anthony Ranalli
Principal Investigator

Dayton

Dayton Children's Hospital

Ayman Ali El-Sheikh
Ph: 800-228-4055

Ayman Ali El-Sheikh
Principal Investigator

Toledo

The Toledo Hospital/Toledo Children's Hospital

Jamie L. Dargart
Ph: 419-824-1842

Jamie L. Dargart
Principal Investigator

Oklahoma
Oklahoma City

University of Oklahoma Health Sciences Center

Rene Yvonne McNall-Knapp
Ph: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu

Rene Yvonne McNall-Knapp
Principal Investigator

Oregon
Portland

Legacy Emanuel Children's Hospital

Janice Faye Olson
Ph: 503-413-2560

Janice Faye Olson
Principal Investigator

Oregon Health and Science University

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

Bill Hoon Chang
Principal Investigator

Pennsylvania
Bethlehem

Lehigh Valley Hospital - Muhlenberg

Philip M. Monteleone
Ph: 484-884-2201

Philip M. Monteleone
Principal Investigator

Danville

Geisinger Medical Center

Jagadeesh Ramdas
Ph: 570-271-5251

Jagadeesh Ramdas
Principal Investigator

Hershey

Penn State Hershey Children's Hospital

Lisa MacNabb McGregor
Ph: 717-531-6012

Lisa MacNabb McGregor
Principal Investigator

Philadelphia

Children's Hospital of Philadelphia

Richard Aplenc
Ph: 215-590-2810

Richard Aplenc
Principal Investigator

Saint Christopher's Hospital for Children

Akash Nahar
Ph: 215-427-8991

Akash Nahar
Principal Investigator

Pittsburgh

Children's Hospital of Pittsburgh of UPMC

Jean M. Tersak
Ph: 412-692-5573

Jean M. Tersak
Principal Investigator

Puerto Rico
San Juan

San Jorge Children's Hospital

Luis A. Clavell
Ph: 787-727-1000

Luis A. Clavell
Principal Investigator

Rhode Island
Providence

Rhode Island Hospital

Jennifer J. Greene Welch
Ph: 401-444-1488

Jennifer J. Greene Welch
Principal Investigator

South Carolina
Charleston

Medical University of South Carolina

Jacqueline M. Kraveka
Ph: 843-792-9321

Jacqueline M. Kraveka
Principal Investigator

Greenville

BI-LO Charities Children's Cancer Center

Nichole Leigh Bryant
Ph: 864-241-6251

Nichole Leigh Bryant
Principal Investigator

South Dakota
Sioux Falls

Sanford USD Medical Center - Sioux Falls

Kayelyn Jean Wagner
Ph: 605-328-1367

Kayelyn Jean Wagner
Principal Investigator

Tennessee
Knoxville

East Tennessee Childrens Hospital

Ray C. Pais
Ph: 865-541-8266

Ray C. Pais
Principal Investigator

Texas
Austin

Dell Children's Medical Center of Central Texas

Amy Catherine Fowler
Ph: 214-648-7097

Amy Catherine Fowler
Principal Investigator

Corpus Christi

Driscoll Children's Hospital

M. Cris Johnson
Ph: 361-694-5311
Email: cris.johnson@dchstx.org

M. Cris Johnson
Principal Investigator

Dallas

Medical City Dallas Hospital

Stanton Carl Goldman
Ph: 972-566-5588

Stanton Carl Goldman
Principal Investigator

UT Southwestern/Simmons Cancer Center-Dallas

Tamra Lynn Slone
Ph: 214-648-7097

Tamra Lynn Slone
Principal Investigator

El Paso

El Paso Children's Hospital

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

Lisa Louise Rubin Hartman
Principal Investigator

Fort Worth

Cook Children's Medical Center

Kenneth Matthew Heym
Ph: 682-885-2103

Kenneth Matthew Heym
Principal Investigator

Houston

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

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

Michele Simmons Redell
Principal Investigator

San Antonio

Children's Hospital of San Antonio

Timothy C. Griffin
Ph: 800-248-1199

Timothy C. Griffin
Principal Investigator

Methodist Children's Hospital of South Texas

Gerardo Quezada
Ph: 210-575-7000

Gerardo Quezada
Principal Investigator

University of Texas Health Science Center at San Antonio

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

Anne-Marie R. Langevin
Principal Investigator

Temple

Scott and White Memorial Hospital

Guy Howard Grayson
Ph: 254-724-5407

Guy Howard Grayson
Principal Investigator

Utah
Salt Lake City

Primary Children's Hospital

Phillip Evan Barnette
Ph: 801-585-5270

Phillip Evan Barnette
Principal Investigator

Vermont
Burlington

University of Vermont College of Medicine

Alan Charles Homans
Ph: 802-656-4101

Alan Charles Homans
Principal Investigator

Virginia
Falls Church

Inova Fairfax Hospital

Marshall A. Schorin
Ph: 703-208-6650
Email: Stephanie.VanBebber@inova.org

Marshall A. Schorin
Principal Investigator

Norfolk

Childrens Hospital-King's Daughters

Eric Jeffrey Lowe
Ph: 757-668-7243

Eric Jeffrey Lowe
Principal Investigator

Richmond

Virginia Commonwealth University/Massey Cancer Center

Christina Marie Wiedl
Ph: 804-628-1939

Christina Marie Wiedl
Principal Investigator

Roanoke

Carilion Clinic Children's Hospital

Mandy Meck Atkinson
Ph: 540-981-7376

Mandy Meck Atkinson
Principal Investigator

Washington
Seattle

Seattle Children's Hospital

Douglas S. Hawkins
Ph: 866-987-2000

Douglas S. Hawkins
Principal Investigator

Spokane

Providence Sacred Heart Medical Center and Children's Hospital

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

Judy L. Felgenhauer
Principal Investigator

Tacoma

Madigan Army Medical Center

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

Melissa Anne Forouhar
Principal Investigator

Mary Bridge Children's Hospital and Health Center

Robert G. Irwin
Ph: 800-552-1419

Robert G. Irwin
Principal Investigator

West Virginia
Morgantown

West Virginia University Healthcare

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

Stephan R. Paul
Principal Investigator

Wisconsin
Green Bay

Saint Vincent Hospital

John Robert Hill
Ph: 920-433-8889

John Robert Hill
Principal Investigator

Madison

University of Wisconsin Hospital and Clinics

Kenneth Brian De Santes
Ph: 715-422-7718

Kenneth Brian De Santes
Principal Investigator

Marshfield

Marshfield Clinic

Michael John McManus
Ph: 715-389-4457

Michael John McManus
Principal Investigator

Milwaukee

Children¿s Hospital of Wisconsin

Richard L. Tower
Ph: 414-805-4380

Richard L. Tower
Principal Investigator

Australia

Hunter Regional Mail Centre

John Hunter Children's Hospital

Draga Barbaric
Ph: (02) 9382-1721

Draga Barbaric
Principal Investigator

Parkville

Royal Children's Hospital

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

Francoise Marie Mechinaud
Principal Investigator

Perth

Princess Margaret Hospital for Children

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

Catherine Helen Cole
Principal Investigator

South Brisbane

Lady Cilento Children's Hospital

Helen Irving
Ph: 1300 762 831

Helen Irving
Principal Investigator

Canada

Alberta
Calgary

Alberta Children's Hospital

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

Douglas R. Strother
Principal Investigator

Manitoba
Winnipeg

CancerCare Manitoba

John Joseph Doyle
Ph: 866-561-1026
Email: CIO_Web@cancercare.mb.ca

John Joseph Doyle
Principal Investigator

Newfoundland and Labrador
Saint John's

Janeway Child Health Centre

Lisa Anne Beresford Goodyear
Ph: 866-722-1126

Lisa Anne Beresford Goodyear
Principal Investigator

Nova Scotia
Halifax

IWK Health Centre

Conrad Vincent Fernandez
Ph: 902-470-8394

Conrad Vincent Fernandez
Principal Investigator

Ontario
Hamilton

Chedoke Hospital at Hamilton Health Sciences

Carol Portwine
Ph: 905-521-2100ext74595

Carol Portwine
Principal Investigator

McMaster Children's Hospital at Hamilton Health Sciences

Carol Portwine
Ph: 905-521-2100extn74595

Carol Portwine
Principal Investigator

Kingston

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Mariana Pradier Silva
Ph: 613-544-2630

Mariana Pradier Silva
Principal Investigator

London

Children's Hospital

Shayna M. Zelcer
Ph: 519-685-8306

Shayna M. Zelcer
Principal Investigator

Ottawa

Children's Hospital of Eastern Ontario

Jacqueline Mary Lewis Halton
Ph: 613-738-3931

Jacqueline Mary Lewis Halton
Principal Investigator

Toronto

Hospital for Sick Children

Sarah Weeks Alexander
Ph: 416-813-7654extn2027
Email: jason.mcguire@sickkids.ca

Sarah Weeks Alexander
Principal Investigator

Quebec
Montreal

Centre Hospitalier Universitaire Sainte-Justine

Yvan Samson
Ph: 514-345-4931

Yvan Samson
Principal Investigator

The Montreal Children's Hospital of the MUHC

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

Sharon Barbara Abish
Principal Investigator

Quebec

Centre Hospitalier Universitaire de Quebec

Bruno Michon
Ph: 888-823-5923
Email: ctsucontact@westat.com

Bruno Michon
Principal Investigator

New Zealand

Christchurch

Christchurch Hospital

Siobhan Frances Cross
Ph: +03 364 0640

Siobhan Frances Cross
Principal Investigator

Grafton

Starship Children's Hospital

Lochie Rodrick Teague
Ph: +0800 728 436

Lochie Rodrick Teague
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01371981

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.