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Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)

RecruitingPhase 3

A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or ALK Inhibitor Therapy Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL)

Who can join

365 Days – 30 Years · All sexes

Full eligibility criteria
Inclusion Criteria:

* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patient must be \>= 365 days and =\< 30 years of age at diagnosis
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:

  * Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:

    * MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
    * Age \> 547 days regardless of biologic features
  * Patients with INRG stage MS disease with MYCN amplification
  * Patients with INRG stage L2 disease with MYCN amplification
  * Patients \> 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
  * Patients \>= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/sex as follows:

  * 1 to \< 2 years: male = 0.6; female = 0.6
  * 2 to \< 6 years: male = 0.8; female = 0.8
  * 6 to \< 10 years: male = 1; female = 1
  * 10 to \< 13 years: male = 1.2; female = 1.2
  * 13 to \< 16 years: male = 1.5; female = 1.4
  * \>= 16 years: male = 1.7; female = 1.4
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \> 50% by echocardiogram or radionuclide angiogram
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): See ANBL2131 (NCT06172296) protocol for eligible high-risk neuroblastoma diagnoses
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In addition, all patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) Arm E must have tumors with an ALK aberration
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Given the lack of data with lorlatinib in infant populations, patients transferring from ANBL2131 (NCT06172296) to ANBL1531 (NCT03126916) must be \> 1 year of age at time of transfer to ANBL1531 (NCT03126916). Patients \< 1 year of age found to have a qualifying ALK alteration as part of ANBL2131 (NCT06172296) may continue to participate in ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients initially recognized to have high-risk disease must have received no more than one cycle of topotecan/cyclophosphamide either after enrollment to ANBL2131 (NCT06172296) or started emergently prior to enrollment to ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received up to one cycle of intermediate risk chemotherapy prior to initial enrollment to ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients may have received localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): In order to facilitate patient transfer and ensure timely distribution of lorlatinib, there are no blood count requirements to meet at time of transfer from ANBL2131 (NCT06172296) to ANBL1531 ((NCT03126916) Arm E. Note the blood count criteria that must be met prior to start of Induction cycle 2 on Arm E. Lorlatinib therapy should start no sooner than day 1 of Induction cycle 2
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known irreversible grade 2 or greater atrioventricular (AV) block
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Due the potential psychiatric risks from lorlatinib, patients should not have a personal history of a serious psychiatric disorder requiring pharmacologic intervention or severe enough to be considered life-threatening
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution deems feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure

Exclusion Criteria:

* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients with bone marrow failure syndromes
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: 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
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Lactating females who plan to breastfeed their infants
* FOR PATIENTS ENROLLING TO ANBL1531 (NCT03126916) WITHOUT PRIOR ANBL2131 (NCT06172296) ENROLLMENT: Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have previously received treatment with lorlatinib or other ALK inhibitor
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have undergone treatment arm randomization callback or started induction cycle 2 on ANBL2131 (NCT06172296)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients who have an INRG Stage L2 tumor without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Patients with bone marrow failure syndromes
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): 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
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Lactating females who plan to breastfeed their infants
* PATIENTS WITH TUMORS HARBORING ALK ALTERATIONS TRANSFERRING TO ANBL1531 (NCT03126916) ARM E FROM ANBL2131 (NCT06172296) (EFFECTIVE WITH AMENDMENT 13C): Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

About the study

This phase III trial studies iobenguane I-131 or lorlatinib and standard therapy in treating younger patients with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma. Radioactive drugs, such as iobenguane I-131, may carry radiation directly to tumor cells and not harm normal cells. Lorlatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or lorlatinib and standard therapy may work better compared to lorlatinib and standard therapy alone in treating younger patients with neuroblastoma or ganglioneuroblastoma.

What is being tested

Sponsor: Children's Oncology Group · Participants: 750 · Started: May 14, 2018

Contact the study team

Official record on ClinicalTrials.gov — NCT03126916

Locations in the U.S.

AlabamaChildren's Hospital of Alabama, Birmingham
ArizonaPhoenix Childrens Hospital, Phoenix
ArkansasArkansas Children's Hospital, Little Rock
CaliforniaKaiser Permanente Downey Medical Center, Downey
Loma Linda University Medical Center, Loma Linda
Children's Hospital Los Angeles, Los Angeles
Mattel Children's Hospital UCLA, Los Angeles
Valley Children's Hospital, Madera
Kaiser Permanente-Oakland, Oakland
Children's Hospital of Orange County, Orange
Lucile Packard Children's Hospital Stanford University, Palo Alto
University of California Davis Comprehensive Cancer Center, Sacramento
Naval Medical Center -San Diego, San Diego
Rady Children's Hospital - San Diego, San Diego
UCSF Medical Center-Mission Bay, San Francisco
ColoradoChildren's Hospital Colorado, Aurora
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center, Denver
ConnecticutConnecticut Children's Medical Center, Hartford
Yale University, New Haven
DelawareAlfred I duPont Hospital for Children, Wilmington
District of ColumbiaChildren's National Medical Center, Washington D.C.
FloridaGolisano Children's Hospital of Southwest Florida, Fort Myers
UF Health Cancer Institute - Gainesville, Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood
Nemours Children's Clinic-Jacksonville, Jacksonville
Nicklaus Children's Hospital, Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami
AdventHealth Orlando, Orlando
Nemours Children's Hospital, Orlando
Johns Hopkins All Children's Hospital, St. Petersburg
Saint Mary's Medical Center, West Palm Beach
GeorgiaChildren's Healthcare of Atlanta - Arthur M Blank Hospital, Atlanta
Memorial Health University Medical Center, Savannah
IdahoSaint Luke's Cancer Institute - Boise, Boise
IllinoisLurie Children's Hospital-Chicago, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
University of Illinois, Chicago
Advocate Children's Hospital-Oak Lawn, Oak Lawn
Advocate Children's Hospital-Park Ridge, Park Ridge
OSF Children's Hospital of Illinois, Peoria
Southern Illinois University School of Medicine, Springfield
IndianaRiley Hospital for Children, Indianapolis
IowaBlank Children's Hospital, Des Moines
University of Iowa/Holden Comprehensive Cancer Center, Iowa City
KentuckyUniversity of Kentucky/Markey Cancer Center, Lexington
LouisianaChildren's Hospital New Orleans, New Orleans
Ochsner Medical Center Jefferson, New Orleans
MaineEastern Maine Medical Center, Bangor
Maine Children's Cancer Program, Scarborough
MarylandJohns Hopkins University/Sidney Kimmel Cancer Center, Baltimore
Sinai Hospital of Baltimore, Baltimore
University of Maryland/Greenebaum Cancer Center, Baltimore
MassachusettsDana-Farber Cancer Institute, Boston
Massachusetts General Hospital Cancer Center, Boston
MichiganC S Mott Children's Hospital, Ann Arbor
Children's Hospital of Michigan, Detroit
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital, Grand Rapids
Bronson Methodist Hospital, Kalamazoo
Corewell Health Children's, Royal Oak
MinnesotaChildren's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis
University of Minnesota/Masonic Cancer Center, Minneapolis
Mayo Clinic in Rochester, Rochester
MississippiUniversity of Mississippi Medical Center, Jackson
MissouriUniversity of Missouri Children's Hospital, Columbia
Children's Mercy Hospitals and Clinics, Kansas City
Mercy Hospital Saint Louis, St Louis
Washington University School of Medicine, St Louis
NebraskaChildren's Hospital and Medical Center of Omaha, Omaha
University of Nebraska Medical Center, Omaha
NevadaAlliance for Childhood Diseases/Cure 4 the Kids Foundation, Las Vegas
Summerlin Hospital Medical Center, Las Vegas
Sunrise Hospital and Medical Center, Las Vegas
University Medical Center of Southern Nevada, Las Vegas
New HampshireDartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon
New JerseyHackensack University Medical Center, Hackensack
Morristown Medical Center, Morristown
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital, New Brunswick
Saint Peter's University Hospital, New Brunswick
Newark Beth Israel Medical Center, Newark
Saint Joseph's Regional Medical Center, Paterson
New MexicoUniversity of New Mexico Cancer Center, Albuquerque
New YorkAlbany Medical Center, Albany
Maimonides Medical Center, Brooklyn
Roswell Park Cancer Institute, Buffalo
NYU Langone Hospital - Long Island, Mineola
The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York
University of Rochester, Rochester
Stony Brook University Medical Center, Stony Brook
State University of New York Upstate Medical University, Syracuse
Montefiore Medical Center - Moses Campus, The Bronx
New York Medical College, Valhalla
North CarolinaMission Hospital, Asheville
UNC Lineberger Comprehensive Cancer Center, Chapel Hill
Carolinas Medical Center/Levine Cancer Institute, Charlotte
Duke University Medical Center, Durham
East Carolina University, Greenville
Wake Forest University Health Sciences, Winston-Salem
North DakotaSanford Broadway Medical Center, Fargo
OhioCincinnati Children's Hospital Medical Center, Cincinnati
Cleveland Clinic Foundation, Cleveland
Rainbow Babies and Childrens Hospital, Cleveland
Nationwide Children's Hospital, Columbus
Dayton Children's Hospital, Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital, Toledo
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
OregonLegacy Emanuel Children's Hospital, Portland
PennsylvaniaLehigh Valley Hospital-Cedar Crest, Allentown
Geisinger Medical Center, Danville
Penn State Children's Hospital, Hershey
Children's Hospital of Philadelphia, Philadelphia
Children's Hospital of Pittsburgh of UPMC, Pittsburgh
Rhode IslandRhode Island Hospital, Providence
South CarolinaMedical University of South Carolina, Charleston
Prisma Health Richland Hospital, Columbia
BI-LO Charities Children's Cancer Center, Greenville
South DakotaSanford USD Medical Center - Sioux Falls, Sioux Falls
TennesseeEast Tennessee Childrens Hospital, Knoxville
Saint Jude Children's Research Hospital, Memphis
The Children's Hospital at TriStar Centennial, Nashville
Vanderbilt University/Ingram Cancer Center, Nashville
TexasDell Children's Medical Center of Central Texas, Austin
Driscoll Children's Hospital, Corpus Christi
UT Southwestern/Simmons Cancer Center-Dallas, Dallas
El Paso Children's Hospital, El Paso
Cook Children's Medical Center, Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston
Covenant Children's Hospital, Lubbock
UMC Cancer Center / UMC Health System, Lubbock
Children's Hospital of San Antonio, San Antonio
Methodist Children's Hospital of South Texas, San Antonio
University of Texas Health Science Center at San Antonio, San Antonio
UtahPrimary Children's Hospital, Salt Lake City
VermontUniversity of Vermont and State Agricultural College, Burlington
WashingtonSeattle Children's Hospital, Seattle
Providence Sacred Heart Medical Center and Children's Hospital, Spokane
Madigan Army Medical Center, Tacoma
Mary Bridge Children's Hospital and Health Center, Tacoma
West VirginiaWest Virginia University Healthcare, Morgantown
WisconsinSaint Vincent Hospital Cancer Center Green Bay, Green Bay
University of Wisconsin Carbone Cancer Center - University Hospital, Madison
Marshfield Medical Center-Marshfield, Marshfield
Children's Hospital of Wisconsin, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Oct 1, 2026. Each study sets its own eligibility; the study team decides who can join.