Clinical trial Recruiting at 153 sites Phase 3 Interventional Ages 365 Days to 30

Adding iobenguane I-131 or lorlatinib to intensive treatment for children and young adults with high-risk neuroblastoma

Official title: 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)

Run by Children's Oncology Group · NCT03126916 · Data updated 2026-11-12

This trial tests whether adding the radioactive drug iobenguane I-131 or the targeted drug lorlatinib to standard intensive therapy helps children and young adults with newly diagnosed high-risk neuroblastoma or nodular ganglioneuroblastoma stay free of disease longer.

More Neuroblastoma trials

Quick facts

PhasePhase 3
Study typeInterventional
Ages365 Days to 30 Years
SexAll
Enrollment750 (estimated)
SponsorChildren's Oncology Group
Research network
Drugs / interventionslorlatinib, chemotherapy, radiation, cyclophosphamide, dinutuximab, doxorubicin
Locations164 sites (Birmingham, Alabama and 163 other locations)
StatusRecruiting
StartedMay 14, 2018
Main results expectedSeptember 30, 2030
Study endsSeptember 30, 2030
Registry record updatedAugust 25, 2026
Trial IDNCT03126916 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are patients aged ≥365 days up to 30 years at diagnosis with newly diagnosed high-risk neuroblastoma or nodular ganglioneuroblastoma who enroll on the required companion COG protocols and have tumor confirmation, with ALK-mutant tumors (VAF ≥ 5%) considered for lorlatinib.

Probably not a fit

Patients with low- or intermediate-risk disease, those younger than one year or older than 30 years at diagnosis, patients ineligible for radiation-based therapy or ASCT, and ALK-negative patients are less likely to benefit from the lorlatinib arm or from the specific 131I-MIBG intervention.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase III, randomized clinical trial that adds iobenguane I-131 during induction therapy prior to tandem autologous stem cell transplantation and offers lorlatinib for patients whose tumors carry activating ALK mutations (VAF ≥ 5%). The primary endpoint is event-free survival (EFS), with secondary endpoints including overall survival, response rates by INRC, and toxicity profiles. Treatments include intensive chemotherapy, autologous hematopoietic stem cell transplantation (BuMel), and procedures such as bone marrow aspiration and biospecimen collection to track response and biology. The trial compares outcomes for patients receiving the 131I-MIBG-containing induction and examines lorlatinib outcomes against a contemporaneous cohort without documented ALK activating mutations.

Why it matters

Potential benefit: If successful, adding iobenguane I-131 or lorlatinib could improve event-free survival and potentially increase cure rates for children with high-risk neuroblastoma.

How similar studies have gone: Prior studies have shown activity of 131I-MIBG in relapsed or refractory neuroblastoma and clinical benefit of ALK inhibitors in ALK-mutant pediatric tumors, but incorporating these agents into a frontline randomized phase III regimen is relatively novel.

Who can join: the full rules

Show full inclusion / exclusion 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

Where it's running

  • Children's Hospital of Alabama
    Birmingham, Alabama, United States
    Recruiting
  • Phoenix Childrens Hospital
    Phoenix, Arizona, United States
    Recruiting
  • Arkansas Children's Hospital
    Little Rock, Arkansas, United States
    Recruiting
  • Kaiser Permanente Downey Medical Center
    Downey, California, United States
    Recruiting
  • Loma Linda University Medical Center
    Loma Linda, California, United States
    Recruiting
  • Children's Hospital Los Angeles
    Los Angeles, California, United States
    Recruiting
Show 44 more locations
  • Mattel Children's Hospital UCLA
    Los Angeles, California, United States
    Recruiting
  • Valley Children's Hospital
    Madera, California, United States
    Recruiting
  • Kaiser Permanente-Oakland
    Oakland, California, United States
    Recruiting
  • Children's Hospital of Orange County
    Orange, California, United States
    Recruiting
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto, California, United States
    Recruiting
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, United States
    Recruiting
  • Rady Children's Hospital - San Diego
    San Diego, California, United States
    Recruiting
  • Naval Medical Center -San Diego
    San Diego, California, United States
    Recruiting
  • UCSF Medical Center-Mission Bay
    San Francisco, California, United States
    Recruiting
  • Children's Hospital Colorado
    Aurora, Colorado, United States
    Recruiting
  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
    Denver, Colorado, United States
    Recruiting
  • Connecticut Children's Medical Center
    Hartford, Connecticut, United States
    Recruiting
  • Yale University
    New Haven, Connecticut, United States
    Recruiting
  • Alfred I duPont Hospital for Children
    Wilmington, Delaware, United States
    Recruiting
  • Children's National Medical Center
    Washington D.C., District of Columbia, United States
    Recruiting
  • Golisano Children's Hospital of Southwest Florida
    Fort Myers, Florida, United States
    Recruiting
  • UF Health Cancer Institute - Gainesville
    Gainesville, Florida, United States
    Recruiting
  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    Hollywood, Florida, United States
    Recruiting
  • Nemours Children's Clinic-Jacksonville
    Jacksonville, Florida, United States
    Recruiting
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida, United States
    Recruiting
  • Nicklaus Children's Hospital
    Miami, Florida, United States
    Recruiting
  • AdventHealth Orlando
    Orlando, Florida, United States
    Recruiting
  • Nemours Children's Hospital
    Orlando, Florida, United States
    Recruiting
  • Johns Hopkins All Children's Hospital
    St. Petersburg, Florida, United States
    Recruiting
  • Saint Mary's Medical Center
    West Palm Beach, Florida, United States
    Recruiting
  • Children's Healthcare of Atlanta - Arthur M Blank Hospital
    Atlanta, Georgia, United States
    Recruiting
  • Memorial Health University Medical Center
    Savannah, Georgia, United States
    Recruiting
  • Saint Luke's Cancer Institute - Boise
    Boise, Idaho, United States
    Recruiting
  • Lurie Children's Hospital-Chicago
    Chicago, Illinois, United States
    Recruiting
  • University of Illinois
    Chicago, Illinois, United States
    Recruiting
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois, United States
    Recruiting
  • Advocate Children's Hospital-Oak Lawn
    Oak Lawn, Illinois, United States
    Recruiting
  • Advocate Children's Hospital-Park Ridge
    Park Ridge, Illinois, United States
    Recruiting
  • OSF Children's Hospital of Illinois
    Peoria, Illinois, United States
    Recruiting
  • Southern Illinois University School of Medicine
    Springfield, Illinois, United States
    Recruiting
  • Riley Hospital for Children
    Indianapolis, Indiana, United States
    Recruiting
  • Blank Children's Hospital
    Des Moines, Iowa, United States
    Recruiting
  • University of Iowa/Holden Comprehensive Cancer Center
    Iowa City, Iowa, United States
    Recruiting
  • University of Kentucky/Markey Cancer Center
    Lexington, Kentucky, United States
    Recruiting
  • Children's Hospital New Orleans
    New Orleans, Louisiana, United States
    Recruiting
  • Ochsner Medical Center Jefferson
    New Orleans, Louisiana, United States
    Recruiting
  • Eastern Maine Medical Center
    Bangor, Maine, United States
    Recruiting
  • Maine Children's Cancer Program
    Scarborough, Maine, United States
    Recruiting
  • University of Maryland/Greenebaum Cancer Center
    Baltimore, Maryland, United States
    Recruiting

+114 more sites. See ClinicalTrials.gov for the full list.

Study contacts

  • Principal investigator: Steven G DuBois — Children's Oncology Group

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.