Clinical Trials / Research Studies
Clinical Trials / Research Studies

ANBL1531: A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL)

Why are we doing this research?


This partially randomized phase III trial studies iobenguane I-131 or crizotinib 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. Crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or crizotinib and standard therapy may work better in treating younger patients with neuroblastoma or ganglioneuroblastoma.


  • Event free survival (EFS) rate [ Time Frame: From the time of randomization or assignment to first episode of disease relapse or progression, first occurrence of a second malignancy, or death, assessed for up to 5 years ]
    • Will be assessed with an intent-to-treat log-rank test comparison of EFS rates. The EFS of patients assigned to the ALK-aberrant crizotinib treatment arm will be compared with an intent-to-treat log-rank test to that of all patients assigned to the ALK wild type portion of the trial, except for those patients randomized to receive iobenguane I-131 (131I-MIBG).

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)

Primary Purpose: Treatment

Who can participate?


Inclusion Criteria:

  • Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL1531
  • 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 age or 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
  • 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
  • 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
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram
  • 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.

Exclusion Criteria:

  • Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for may meet criteria for high risk classification but are not eligible for this trial)
  • Patients with bone marrow failure syndromes
  • Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
  • Female patients who are pregnant; 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.


  • 365 days to 30 Years


  • Neuroblastoma New Diagnosis
  • Adult - Neuroblastoma New Diagnosis


Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799