Back to Trials
NCT05304585PHASE3Recruiting

Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma

Children's Oncology Group

Start Date

8/4/2022

Completion Date

6/30/2030

Summary

Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate the failure free survival (FFS) of patients with very low-risk (VLR) rhabdomyosarcoma (RMS) (fusion negative \[FN\], stage 1, clinical group \[CG\] I, MYOD1 wildtype \[WT\], TP53 \[WT\]) when treated with 24 weeks of vincristine and dactinomycin (VA). II. To evaluate the FFS of patients with low-risk (LR) RMS (FN, stage 1 CG II, or stage 2 CG I/II or CG III \[orbit only\], MYOD1 WT, TP53 WT) when treated with 12 weeks of vincristine, dactinomycin and cyclophosphamide (VAC) followed by 12 weeks of VA. SECONDARY OBJECTIVES: I. To evaluate the overall survival (OS) of patients with VLR RMS treated with 24 weeks of VA. II. To evaluate the OS of patients with LR RMS treated with 12 weeks of VAC followed by 12 weeks of VA. III. To demonstrate the feasibility of central molecular risk stratification of patients with newly diagnosed RMS in the context of a prospective clinical trial. EXPLORATORY OBJECTIVES: I. To collect blood and tissue samples for banking at baseline, during treatment, at the end of therapy, and at the time of progression to bank for future research. II. To describe the methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma. III. To describe the outcomes of patients with VLR or LR RMS and MYOD1 or TP53 mutations treated with intensified therapy. OUTLINE: Patients are assigned to 1 of 2 regimens based on clinical features. Patients with positive mutation status are transitioned to a third regimen, Regimen M. REGIMEN VA: Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). REGIMEN VAC/VA: Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Patients may also undergo radiation therapy at cycle 5. REGIMEN M: Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan, positron emission tomography (PET) scan and tumor biopsy throughout the study.

Eligibility Criteria

Age Range: No minimum to 21 years

Inclusion Criteria: * All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial). * Patients must be =\< 21 years at the time of enrollment. * Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients. * All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed. * Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease. * Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease. * Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients \>= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging. * Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors. * Clinically or radiographically enlarged nodes must be sampled for histologic evaluation. * Patients must have a Lansky (for patients =\< 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of \>= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score. * Peripheral absolute neutrophil count (ANC) \>= 750/uL (within 7 days prior to enrollment). * Platelet count \>= 75,000/uL (transfusion independent) (within 7 days prior to enrollment). * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows: * Age: 1 month to \< 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female) * Age: 6 months to \< 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female) * Age: 1 to \< 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female) * Age: 2 to \< 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female) * Age: 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female) * Age: 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female) * Age: 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female) * Age \>= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age. * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L. * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L * 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 who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted. * Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy. * Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment. * Patients unable to undergo radiation therapy, if necessary, as specified in the protocol. * Evidence of uncontrolled infection. * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential. * Lactating females who plan to breastfeed their infants. * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.

Interventions

PROCEDURE

Biopsy Procedure

PROCEDURE

Bone Scan

PROCEDURE

Computed Tomography

DRUG

Cyclophosphamide

BIOLOGICAL

Dactinomycin

PROCEDURE

Magnetic Resonance Elastography

PROCEDURE

Positron Emission Tomography

RADIATION

Radiation Therapy

DRUG

Vincristine

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Embryonal RhabdomyosarcomaFusion-Negative Alveolar RhabdomyosarcomaSpindle Cell/Sclerosing Rhabdomyosarcoma

Locations

Children's Hospital of Alabama

Birmingham, Alabama 35233

United States

USA Health Strada Patient Care Center

Mobile, Alabama 36604

United States

Phoenix Childrens Hospital

Phoenix, Arizona 85016

United States

Arkansas Children's Hospital

Little Rock, Arkansas 72202-3591

United States

Kaiser Permanente Downey Medical Center

Downey, California 90242

United States

Loma Linda University Medical Center

Loma Linda, California 92354

United States

Miller Children's and Women's Hospital Long Beach

Long Beach, California 90806

United States

Children's Hospital Los Angeles

Los Angeles, California 90027

United States

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

Mattel Children's Hospital UCLA

Los Angeles, California 90095

United States

Valley Children's Hospital

Madera, California 93636

United States

UCSF Benioff Children's Hospital Oakland

Oakland, California 94609

United States

Kaiser Permanente-Oakland

Oakland, California 94611

United States

Children's Hospital of Orange County

Orange, California 92868

United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California 94304

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

Rady Children's Hospital - San Diego

San Diego, California 92123

United States

Naval Medical Center -San Diego

San Diego, California 92134

United States

UCSF Medical Center-Mission Bay

San Francisco, California 94158

United States

Children's Hospital Colorado

Aurora, Colorado 80045

United States

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

Denver, Colorado 80218

United States

Connecticut Children's Medical Center

Hartford, Connecticut 06106

United States

Yale University

New Haven, Connecticut 06520

United States

Alfred I duPont Hospital for Children

Wilmington, Delaware 19803

United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia 20007

United States

Children's National Medical Center

Washington D.C., District of Columbia 20010

United States

Broward Health Medical Center

Fort Lauderdale, Florida 33316

United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida 33908

United States

UF Health Cancer Institute - Gainesville

Gainesville, Florida 32610

United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida 33021

United States

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida 32207

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida 33136

United States

Nicklaus Children's Hospital

Miami, Florida 33155

United States

AdventHealth Orlando

Orlando, Florida 32803

United States

Arnold Palmer Hospital for Children

Orlando, Florida 32806

United States

Nemours Children's Hospital

Orlando, Florida 32827

United States

Nemours Children's Clinic - Pensacola

Pensacola, Florida 32504

United States

Sacred Heart Hospital

Pensacola, Florida 32504

United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida 33701

United States

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

Tampa, Florida 33607

United States

Saint Mary's Medical Center

West Palm Beach, Florida 33407

United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia 30329

United States

Atrium Health Navicent

Macon, Georgia 31201

United States

Memorial Health University Medical Center

Savannah, Georgia 31404

United States

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii 96826

United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho 83712

United States

Lurie Children's Hospital-Chicago

Chicago, Illinois 60611

United States

University of Illinois

Chicago, Illinois 60612

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois 60637

United States

Loyola University Medical Center

Maywood, Illinois 60153

United States

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois 60453

United States

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois 60068

United States

Saint Jude Midwest Affiliate

Peoria, Illinois 61637

United States

Southern Illinois University School of Medicine

Springfield, Illinois 62702

United States

Northwestern Medicine Central DuPage Hospital

Winfield, Illinois 60190

United States

Riley Hospital for Children

Indianapolis, Indiana 46202

United States

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana 46260

United States

Blank Children's Hospital

Des Moines, Iowa 50309

United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa 52242

United States

Wesley Medical Center

Wichita, Kansas 67214

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky 40536

United States

Norton Children's Hospital

Louisville, Kentucky 40202

United States

Children's Hospital New Orleans

New Orleans, Louisiana 70118

United States

Ochsner Medical Center Jefferson

New Orleans, Louisiana 70121

United States

Maine Children's Cancer Program

Scarborough, Maine 04074

United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland 21201

United States

Sinai Hospital of Baltimore

Baltimore, Maryland 21215

United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland 21287

United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts 01655

United States

C S Mott Children's Hospital

Ann Arbor, Michigan 48109

United States

Children's Hospital of Michigan

Detroit, Michigan 48201

United States

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan 49503

United States

Bronson Methodist Hospital

Kalamazoo, Michigan 49007

United States

Corewell Health Children's

Royal Oak, Michigan 48073

United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota 55404

United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota 55455

United States

Mayo Clinic in Rochester

Rochester, Minnesota 55905

United States

University of Mississippi Medical Center

Jackson, Mississippi 39216

United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri 64108

United States

Cardinal Glennon Children's Medical Center

St Louis, Missouri 63104

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Mercy Hospital Saint Louis

St Louis, Missouri 63141

United States

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska 68114

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada 89135

United States

Summerlin Hospital Medical Center

Las Vegas, Nevada 89144

United States

Renown Regional Medical Center

Reno, Nevada 89502

United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire 03756

United States

Hackensack University Medical Center

Hackensack, New Jersey 07601

United States

Morristown Medical Center

Morristown, New Jersey 07960

United States

Jersey Shore Medical Center

Neptune City, New Jersey 07753

United States

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey 08903

United States

Newark Beth Israel Medical Center

Newark, New Jersey 07112

United States

University of New Mexico Cancer Center

Albuquerque, New Mexico 87106

United States

Albany Medical Center

Albany, New York 12208

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

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

New Hyde Park, New York 11040

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York 10016

United States

Mount Sinai Hospital

New York, New York 10029

United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

University of Rochester

Rochester, New York 14642

United States

State University of New York Upstate Medical University

Syracuse, New York 13210

United States

Montefiore Medical Center - Moses Campus

The Bronx, New York 10467

United States

New York Medical College

Valhalla, New York 10595

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina 27599

United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina 28203

United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina 28204

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

East Carolina University

Greenville, North Carolina 27834

United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina 27157

United States

Sanford Broadway Medical Center

Fargo, North Dakota 58122

United States

Children's Hospital Medical Center of Akron

Akron, Ohio 44308

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229

United States

Rainbow Babies and Childrens Hospital

Cleveland, Ohio 44106

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

Nationwide Children's Hospital

Columbus, Ohio 43205

United States

Dayton Children's Hospital

Dayton, Ohio 45404

United States

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio 43606

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania 18103

United States

Geisinger Medical Center

Danville, Pennsylvania 17822

United States

Penn State Children's Hospital

Hershey, Pennsylvania 17033

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania 19104

United States

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania 19134

United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania 15224

United States

Rhode Island Hospital

Providence, Rhode Island 02903

United States

Prisma Health Richland Hospital

Columbia, South Carolina 29203

United States

BI-LO Charities Children's Cancer Center

Greenville, South Carolina 29605

United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota 57117-5134

United States

East Tennessee Childrens Hospital

Knoxville, Tennessee 37916

United States

Saint Jude Children's Research Hospital

Memphis, Tennessee 38105

United States

The Children's Hospital at TriStar Centennial

Nashville, Tennessee 37203

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee 37232

United States

Dell Children's Medical Center of Central Texas

Austin, Texas 78723

United States

Driscoll Children's Hospital

Corpus Christi, Texas 78411

United States

Medical City Dallas Hospital

Dallas, Texas 75230

United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas 75390

United States

El Paso Children's Hospital

El Paso, Texas 79905

United States

Cook Children's Medical Center

Fort Worth, Texas 76104

United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas 77030

United States

M D Anderson Cancer Center

Houston, Texas 77030

United States

Covenant Children's Hospital

Lubbock, Texas 79410

United States

UMC Cancer Center / UMC Health System

Lubbock, Texas 79415

United States

Children's Hospital of San Antonio

San Antonio, Texas 78207

United States

Methodist Children's Hospital of South Texas

San Antonio, Texas 78229

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229

United States

Scott and White Memorial Hospital

Temple, Texas 76508

United States

Primary Children's Hospital

Salt Lake City, Utah 84113

United States

University of Virginia Cancer Center

Charlottesville, Virginia 22908

United States

Inova Fairfax Hospital

Falls Church, Virginia 22042

United States

Children's Hospital of The King's Daughters

Norfolk, Virginia 23507

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia 23298

United States

Carilion Children's

Roanoke, Virginia 24014

United States

Seattle Children's Hospital

Seattle, Washington 98105

United States

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington 99204

United States

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington 98405

United States

Madigan Army Medical Center

Tacoma, Washington 98431

United States

West Virginia University Charleston Division

Charleston, West Virginia 25304

United States

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin 53792

United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin 54449

United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin 53226

United States

Sydney Children's Hospital

Randwick, New South Wales 2031

Australia

The Children's Hospital at Westmead

Westmead, New South Wales 2145

Australia

Perth Children's Hospital

Perth, Western Australia 6009

Australia

Alberta Children's Hospital

Calgary, Alberta T3B 6A8

Canada

University of Alberta Hospital

Edmonton, Alberta T6G 2B7

Canada

British Columbia Children's Hospital

Vancouver, British Columbia V6H 3V4

Canada

CancerCare Manitoba

Winnipeg, Manitoba R3E 0V9

Canada

IWK Health Centre

Halifax, Nova Scotia B3K 6R8

Canada

Hospital for Sick Children

Toronto, Ontario M5G 1X8

Canada

The Montreal Children's Hospital of the MUHC

Montreal, Quebec H3H 1P3

Canada

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec H3T 1C5

Canada

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec J1H 5N4

Canada

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Québec, G1V 4G2

Canada

Starship Children's Hospital

Grafton, Auckland 1145

New Zealand

Christchurch Hospital

Christchurch, 8011

New Zealand