Taking people in United StatesPhase 3

Adds iobenguane I-131 or lorlatinib to standard therapy for high-risk neuroblastoma

Tests iobenguane I-131 or lorlatinib added to standard therapy in children with neuroblastoma.

Plain-language title generated from the registry record
Registry title: Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)

Key facts

Where: Albany, Albuquerque, Allentown, Ann Arbor, Asheville, Atlanta, Aurora, Austin, Baltimore, Bangor, Bethesda, Birmingham, Boise, Boston, Brooklyn, Buffalo, Burlington, Chapel Hill, Charleston, Charlotte, Chicago, Cincinnati, Cleveland, Columbia, Columbus, Corpus Christi, Dallas, Danville, Dayton, Denver, Des Moines, Detroit, Downey, Durham, East Lansing, El Paso, Fargo, Fort Myers, Fort Worth, Gainesville, Grand Rapids, Green Bay, Greenville, Hackensack, Hartford, Hershey, Hollywood, Honolulu, Houston, Indianapolis, Iowa City, Jackson, Jacksonville, Kalamazoo, Kansas City, Knoxville, Las Vegas, Lebanon, Lexington, Little Rock, Loma Linda, Los Angeles, Lubbock, Madera, Madison, Marshfield, Memphis, Miami, Milwaukee, Mineola, Minneapolis, Morgantown, Morristown, Nashville, New Brunswick, New Haven, New Hyde Park, New Orleans, New York, Newark, Oak Lawn, Oakland, Oklahoma City, Omaha, Orange, Orlando, Palo Alto, Park Ridge, Paterson, Peoria, Philadelphia, Phoenix, Pittsburgh, Portland, Providence, Richmond, Rochester, Royal Oak, Sacramento, Salt Lake City, San Antonio, San Diego, San Francisco, Savannah, Scarborough, Seattle, Sioux Falls, Spokane, Springfield, St Louis, St. Petersburg, Stony Brook, Syracuse, Tacoma, The Bronx, Toledo, Valhalla, Washington D.C., West Palm Beach, Wilmington, and Winston-Salem, United StatesSee the 152 sites
Phase: Phase 3

AI summary: who the study is looking for

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for children and young adults with newly diagnosed high-risk neuroblastoma or nodular ganglioneuroblastoma, to test adding iobenguane I-131 or lorlatinib to standard intensive therapy.

Age: At least 365 days and up to 30 years old at diagnosis.
Sex: All sexes can join.
Disease stage: Neuroblastoma or nodular ganglioneuroblastoma confirmed by tumor pathology or bone marrow findings with raised urine catecholamine metabolites. INRG stage M disease with MYCN amplification or age over 547 days; stage MS or L2 disease with MYCN amplification; or earlier stage L1, L2 or MS disease that progressed to stage M within the stated limits.
Earlier treatment: No prior systemic therapy for high-risk disease, except topotecan/cyclophosphamide started in an emergency, one cycle of low or intermediate risk chemotherapy, or localized emergency radiation. No earlier lorlatinib or other ALK inhibitor for people transferring from ANBL2131.
Biomarker or test result: MYCN amplification (more than 4-fold increase in MYCN signals) is one way in. People transferring from ANBL2131 to Arm E must have a tumor with an ALK change.

Main reasons for not taking part

INRG stage L2 tumor without MYCN amplification
Bone marrow failure syndromes
Pregnancy, or breastfeeding with plans to continue
Medical disorders that make targeted radiopharmaceutical therapy unsafe
Not agreeing to use effective contraception if sexually active and able to have children

Read by machine on 12 November 2026.

Where in United States

Albany Medical CenterAlbany, United StatesContact: Lauren R. Weintraub (principal investigator)Taking people
University of New Mexico Cancer CenterAlbuquerque, United StatesContact: Jessica M. Valdez (principal investigator)Taking people
Lehigh Valley Hospital-Cedar CrestAllentown, United StatesContact: Jacob A. Troutman (principal investigator)Taking people
C S Mott Children's HospitalAnn Arbor, United StatesContact: Rajen Mody (principal investigator)Taking people
Mission HospitalAsheville, United StatesContact: Douglas J. Scothorn (principal investigator)Taking people
Children's Healthcare of Atlanta - Arthur M Blank HospitalAtlanta, United StatesContact: William T. Cash (principal investigator)Taking people
Children's Hospital ColoradoAurora, United StatesContact: Margaret E. Macy (principal investigator)Taking people
Dell Children's Medical Center of Central TexasAustin, United StatesContact: Shannon M. Cohn (principal investigator)Taking people
Johns Hopkins University/Sidney Kimmel Cancer CenterBaltimore, United StatesContact: Allen R. Chen (principal investigator)Taking people
Sinai Hospital of BaltimoreBaltimore, United StatesContact: Jason M. Fixler (principal investigator)Taking people
University of Maryland/Greenebaum Cancer CenterBaltimore, United StatesContact: Teresa A. York (principal investigator)Taking people
Eastern Maine Medical CenterBangor, United StatesTaking people
Walter Reed National Military Medical CenterBethesda, United StatesNo longer taking part
Children's Hospital of AlabamaBirmingham, United StatesContact: Elizabeth D. Alva (principal investigator)Taking people
Saint Luke's Cancer Institute - BoiseBoise, United StatesContact: Martha M. Pacheco (principal investigator)Taking people
Dana-Farber Cancer InstituteBoston, United StatesContact: Suzanne Shusterman (principal investigator)Taking people
Massachusetts General Hospital Cancer CenterBoston, United StatesContact: Suzanne Shusterman (principal investigator)Taking people
Tufts Children's HospitalBoston, United StatesNo longer taking part
Maimonides Medical CenterBrooklyn, United StatesContact: Mahmut Y. Celiker (principal investigator)Taking people
Roswell Park Cancer InstituteBuffalo, United StatesContact: Clare J. Twist (principal investigator)Taking people
University of Vermont and State Agricultural CollegeBurlington, United StatesContact: Jessica L. Heath (principal investigator)Taking people
UNC Lineberger Comprehensive Cancer CenterChapel Hill, United StatesContact: Thomas B. Alexander (principal investigator)Taking people
Medical University of South CarolinaCharleston, United StatesContact: Jacqueline M. Kraveka (principal investigator)Taking people
Carolinas Medical Center/Levine Cancer InstituteCharlotte, United StatesContact: Joel A. Kaplan (principal investigator)Taking people
Lurie Children's Hospital-ChicagoChicago, United StatesContact: Elizabeth A. Sokol (principal investigator)Taking people
University of Chicago Comprehensive Cancer CenterChicago, United StatesContact: Susan L. Cohn (principal investigator)Taking people
University of IllinoisChicago, United StatesContact: Dipti S. Dighe (principal investigator)Taking people
Cincinnati Children's Hospital Medical CenterCincinnati, United StatesContact: Robin E. Norris (principal investigator)Taking people
Cleveland Clinic FoundationCleveland, United StatesContact: Matteo M. Trucco (principal investigator)Taking people
Rainbow Babies and Childrens HospitalCleveland, United StatesContact: Duncan S. Stearns (principal investigator)Taking people
Prisma Health Richland HospitalColumbia, United StatesContact: Stuart L. Cramer (principal investigator)Taking people
University of Missouri Children's HospitalColumbia, United StatesContact: Barbara A. Gruner (principal investigator)Taking people
Nationwide Children's HospitalColumbus, United StatesContact: Mark A. Ranalli (principal investigator)Taking people
Driscoll Children's HospitalCorpus Christi, United StatesContact: Nkechi I. Mba (principal investigator)Taking people
UT Southwestern/Simmons Cancer Center-DallasDallas, United StatesContact: Tanya C. Watt (principal investigator)Taking people
Medical City Dallas HospitalDallas, United StatesNo longer taking part
Geisinger Medical CenterDanville, United StatesContact: Jagadeesh Ramdas (principal investigator)Taking people
Dayton Children's HospitalDayton, United StatesContact: Jordan M. Wright (principal investigator)Taking people
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterDenver, United StatesContact: Florence Choo (principal investigator)Taking people
Blank Children's HospitalDes Moines, United StatesContact: Samantha L. Mallory (principal investigator)Taking people
Children's Hospital of MichiganDetroit, United StatesContact: Roland L. Chu (principal investigator)Taking people
Henry Ford Health Saint John HospitalDetroit, United StatesNo longer taking part
Wayne State University/Karmanos Cancer InstituteDetroit, United StatesNo longer taking part
Kaiser Permanente Downey Medical CenterDowney, United StatesContact: Robert M. Cooper (principal investigator)Taking people
Duke University Medical CenterDurham, United StatesContact: Jessica M. Sun (principal investigator)Taking people
Michigan State UniversityEast Lansing, United StatesNo longer taking part
El Paso Children's HospitalEl Paso, United StatesContact: Benjamin Carcamo (principal investigator)Taking people
Sanford Broadway Medical CenterFargo, United StatesContact: Samuel J. Milanovich (principal investigator)Taking people
Golisano Children's Hospital of Southwest FloridaFort Myers, United StatesContact: Emad K. Salman (principal investigator)Taking people
Cook Children's Medical CenterFort Worth, United StatesContact: Chelsee Greer (principal investigator)Taking people
UF Health Cancer Institute - GainesvilleGainesville, United StatesContact: Brian Stover (principal investigator)Taking people
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's HospitalGrand Rapids, United StatesContact: Kathleen Y. Butler (principal investigator)Taking people
Saint Vincent Hospital Cancer Center Green BayGreen Bay, United StatesContact: Catherine A. Long (principal investigator)Taking people
BI-LO Charities Children's Cancer CenterGreenville, United StatesContact: Aniket Saha (principal investigator)Taking people
East Carolina UniversityGreenville, United StatesContact: Andrea R. Whitfield (principal investigator)Taking people
Hackensack University Medical CenterHackensack, United StatesContact: Katharine Offer (principal investigator)Taking people
Connecticut Children's Medical CenterHartford, United StatesContact: Michael S. Isakoff (principal investigator)Taking people
Penn State Children's HospitalHershey, United StatesContact: Lisa M. McGregor (principal investigator)Taking people
Memorial Regional Hospital/Joe DiMaggio Children's HospitalHollywood, United StatesContact: Iftikhar Hanif (principal investigator)Taking people
Kapiolani Medical Center for Women and ChildrenHonolulu, United StatesNo longer taking part
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterHouston, United StatesContact: Jennifer H. Foster (principal investigator)Taking people
Riley Hospital for ChildrenIndianapolis, United StatesContact: Sandeep Batra (principal investigator)Taking people
University of Iowa/Holden Comprehensive Cancer CenterIowa City, United StatesContact: Andrew P. Groves (principal investigator)Taking people
University of Mississippi Medical CenterJackson, United StatesContact: Amanda Strobel (principal investigator)Taking people
Nemours Children's Clinic-JacksonvilleJacksonville, United StatesContact: Vibhuti Agarwal (principal investigator)Taking people
Bronson Methodist HospitalKalamazoo, United StatesContact: Kathleen Y. Butler (principal investigator)Taking people
Children's Mercy Hospitals and ClinicsKansas City, United StatesContact: Keith J. August (principal investigator)Taking people
East Tennessee Childrens HospitalKnoxville, United StatesContact: Susan E. Spiller (principal investigator)Taking people
Alliance for Childhood Diseases/Cure 4 the Kids FoundationLas Vegas, United StatesContact: Alan K. Ikeda (principal investigator)Taking people
Summerlin Hospital Medical CenterLas Vegas, United StatesContact: Alan K. Ikeda (principal investigator)Taking people
Sunrise Hospital and Medical CenterLas Vegas, United StatesContact: Alan K. Ikeda (principal investigator)Taking people
University Medical Center of Southern NevadaLas Vegas, United StatesContact: Alan K. Ikeda (principal investigator)Taking people
Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterLebanon, United StatesContact: Angela Ricci (principal investigator)Taking people
University of Kentucky/Markey Cancer CenterLexington, United StatesContact: James T. Badgett (principal investigator)Taking people
Arkansas Children's HospitalLittle Rock, United StatesContact: Michael W. Bishop (principal investigator)Taking people
Loma Linda University Medical CenterLoma Linda, United StatesContact: Albert Kheradpour (principal investigator)Taking people
Children's Hospital Los AngelesLos Angeles, United StatesContact: Araz Marachelian (principal investigator)Taking people
Mattel Children's Hospital UCLALos Angeles, United StatesContact: Satiro N. De Oliveira (principal investigator)Taking people
Covenant Children's HospitalLubbock, United StatesContact: Kishor M. Bhende (principal investigator)Taking people
UMC Cancer Center / UMC Health SystemLubbock, United StatesContact: Erin K. Barr (principal investigator)Taking people
Valley Children's HospitalMadera, United StatesContact: Ruetima Titapiwatanakun (principal investigator)Taking people
University of Wisconsin Carbone Cancer Center - University HospitalMadison, United StatesContact: Margo L. Hoover-Regan (principal investigator)Taking people
Marshfield Medical Center-MarshfieldMarshfield, United StatesContact: Michelle A. Manalang (principal investigator)Taking people
Saint Jude Children's Research HospitalMemphis, United StatesContact: Sara M. Federico (principal investigator)Taking people
Nicklaus Children's HospitalMiami, United StatesContact: Maggie E. Fader (principal investigator)Taking people
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, United StatesContact: Meghan McCormick (principal investigator)Taking people
Children's Hospital of WisconsinMilwaukee, United StatesContact: Angela Steineck (principal investigator)Taking people
NYU Langone Hospital - Long IslandMineola, United StatesContact: Chana L. Glasser (principal investigator)Taking people
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, United StatesContact: Michael K. Richards (principal investigator)Taking people
University of Minnesota/Masonic Cancer CenterMinneapolis, United StatesContact: Robin L. Williams (principal investigator)Taking people
West Virginia University HealthcareMorgantown, United StatesContact: Ashley E. Meyer (principal investigator)Taking people
Morristown Medical CenterMorristown, United StatesContact: Kathryn L. Laurie (principal investigator)Taking people
The Children's Hospital at TriStar CentennialNashville, United StatesContact: Clinton M. Carroll (principal investigator)Taking people
Vanderbilt University/Ingram Cancer CenterNashville, United StatesContact: Daniel J. Benedetti (principal investigator)Taking people
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University HospitalNew Brunswick, United StatesContact: Nehal S. Parikh (principal investigator)Taking people
Saint Peter's University HospitalNew Brunswick, United StatesContact: Nibal A. Zaghloul (principal investigator)Taking people
Yale UniversityNew Haven, United StatesContact: Farzana Pashankar (principal investigator)Taking people
The Steven and Alexandra Cohen Children's Medical Center of New YorkNew Hyde Park, United StatesContact: Julie I. Krystal (principal investigator)Taking people
Children's Hospital New OrleansNew Orleans, United StatesContact: Maria C. Velez-Yanguas (principal investigator)Taking people
Ochsner Medical Center JeffersonNew Orleans, United StatesContact: Craig Lotterman (principal investigator)Taking people
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterNew York, United StatesContact: Nobuko Hijiya (principal investigator)Taking people
Laura and Isaac Perlmutter Cancer Center at NYU LangoneNew York, United StatesNo longer taking part
Newark Beth Israel Medical CenterNewark, United StatesContact: Teena Bhatla (principal investigator)Taking people
Advocate Children's Hospital-Oak LawnOak Lawn, United StatesContact: Rebecca E. McFall (principal investigator)Taking people
Kaiser Permanente-OaklandOakland, United StatesContact: Aarati V. Rao (principal investigator)Taking people
University of Oklahoma Health Sciences CenterOklahoma City, United StatesContact: Rene Y. McNall-Knapp (principal investigator)Taking people
Children's Hospital and Medical Center of OmahaOmaha, United StatesContact: Jill C. Beck (principal investigator)Taking people
University of Nebraska Medical CenterOmaha, United StatesContact: Jill C. Beck (principal investigator)Taking people
Children's Hospital of Orange CountyOrange, United StatesContact: Elyssa M. Rubin (principal investigator)Taking people
AdventHealth OrlandoOrlando, United StatesContact: Fouad M. Hajjar (principal investigator)Taking people
Nemours Children's HospitalOrlando, United StatesContact: Vibhuti Agarwal (principal investigator)Taking people
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, United StatesContact: Jay Michael S. Balagtas (principal investigator)Taking people
Advocate Children's Hospital-Park RidgePark Ridge, United StatesContact: Rebecca E. McFall (principal investigator)Taking people
Saint Joseph's Regional Medical CenterPaterson, United StatesContact: Alissa Kahn (principal investigator)Taking people
OSF Children's Hospital of IllinoisPeoria, United StatesContact: Prerna Kumar (principal investigator)Taking people
Children's Hospital of PhiladelphiaPhiladelphia, United StatesContact: Rochelle Bagatell (principal investigator)Taking people
Phoenix Childrens HospitalPhoenix, United StatesContact: Francis K. Eshun (principal investigator)Taking people
Children's Hospital of Pittsburgh of UPMCPittsburgh, United StatesContact: Jean M. Tersak (principal investigator)Taking people
Legacy Emanuel Children's HospitalPortland, United StatesContact: Jason M. Glover (principal investigator)Taking people
Rhode Island HospitalProvidence, United StatesContact: Bradley DeNardo (principal investigator)Taking people
VCU Massey Comprehensive Cancer CenterRichmond, United StatesNo longer taking part
Mayo Clinic in RochesterRochester, United StatesContact: Wendy Allen-Rhoades (principal investigator)Taking people
University of RochesterRochester, United StatesContact: Jeffrey R. Andolina (principal investigator)Taking people
Corewell Health Children'sRoyal Oak, United StatesContact: Marie V. Nelson (principal investigator)Taking people
University of California Davis Comprehensive Cancer CenterSacramento, United StatesContact: Marcio H. Malogolowkin (principal investigator)Taking people
Primary Children's HospitalSalt Lake City, United StatesContact: Leonora R. Slatnick (principal investigator)Taking people
Children's Hospital of San AntonioSan Antonio, United StatesContact: Julie Voeller (principal investigator)Taking people
Methodist Children's Hospital of South TexasSan Antonio, United StatesContact: Jose M. Esquilin (principal investigator)Taking people
University of Texas Health Science Center at San AntonioSan Antonio, United StatesContact: Anne-Marie R. Langevin (principal investigator)Taking people
Naval Medical Center -San DiegoSan Diego, United StatesContact: Yoko T. Udaka (principal investigator)Taking people
Rady Children's Hospital - San DiegoSan Diego, United StatesContact: William D. Roberts (principal investigator)Taking people
UCSF Medical Center-Mission BaySan Francisco, United StatesContact: Kieuhoa T. Vo (principal investigator)Taking people
Memorial Health University Medical CenterSavannah, United StatesContact: Andrew L. Pendleton (principal investigator)Taking people
Maine Children's Cancer ProgramScarborough, United StatesContact: Eric C. Larsen (principal investigator)Taking people
Seattle Children's HospitalSeattle, United StatesContact: Sarah E. Leary (principal investigator)Taking people
Sanford USD Medical Center - Sioux FallsSioux Falls, United StatesContact: Jordan Fritch-Hanson (principal investigator)Taking people
Providence Sacred Heart Medical Center and Children's HospitalSpokane, United StatesContact: Judy L. Felgenhauer (principal investigator)Taking people
Southern Illinois University School of MedicineSpringfield, United StatesContact: Gregory P. Brandt (principal investigator)Taking people
Mercy Hospital Saint LouisSt Louis, United StatesContact: Robin D. Hanson (principal investigator)Taking people
Washington University School of MedicineSt Louis, United StatesContact: Frederick S. Huang (principal investigator)Taking people
Johns Hopkins All Children's HospitalSt. Petersburg, United StatesContact: Jennifer B. Dean (principal investigator)Taking people
Stony Brook University Medical CenterStony Brook, United StatesContact: Laura E. Hogan (principal investigator)Taking people
State University of New York Upstate Medical UniversitySyracuse, United StatesContact: Melanie A. Comito (principal investigator)Taking people
Madigan Army Medical CenterTacoma, United StatesContact: Melissa A. Forouhar (principal investigator)Taking people
Mary Bridge Children's Hospital and Health CenterTacoma, United StatesContact: Robert G. Irwin (principal investigator)Taking people
Montefiore Medical Center - Moses CampusThe Bronx, United StatesContact: Alice Lee (principal investigator)Taking people
ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalToledo, United StatesContact: Jamie L. Dargart (principal investigator)Taking people
New York Medical CollegeValhalla, United StatesContact: Andrew J. Bellantoni (principal investigator)Taking people
Children's National Medical CenterWashington D.C., United StatesContact: Jeffrey S. Dome (principal investigator)Taking people
Saint Mary's Medical CenterWest Palm Beach, United StatesContact: Matthew D. Ramirez (principal investigator)Taking people
Alfred I duPont Hospital for ChildrenWilmington, United StatesContact: Vibhuti Agarwal (principal investigator)Taking people
Wake Forest University Health SciencesWinston-Salem, United StatesContact: Sarah Supples (principal investigator)Taking people

Questions to ask the study team

How often do I need to come in, and for how long each time?
Are travel costs paid?
Can I keep my own doctor?
What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Trial details

Who runs it: Children's Oncology Group
Trial code: NCT03126916
Record updated: 25 August 2026
Original description: 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.Read full original descriptionShow less
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)
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.
Inclusion: 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: 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): 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): 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): 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): 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.
ClinicalTrials.gov NCT03126916