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

Not Recruiting

Trial ID: NCT03126916


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.

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)

Stanford Investigator(s)


Inclusion Criteria:

   - Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to
   enrollment on ANBL1531 (NCT03126916)

   - Patient must be >= 365 days and =< 30 years of age at diagnosis

   - 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

   - 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 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 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


procedure: Autologous Hematopoietic Stem Cell Transplantation

drug: Busulfan

drug: Carboplatin

drug: Cisplatin

drug: Cyclophosphamide

drug: Dexrazoxane Hydrochloride

biological: Dinutuximab

drug: Doxorubicin Hydrochloride

drug: Etoposide Phosphate

radiation: External Beam Radiation Therapy

radiation: Iobenguane I-131

drug: Isotretinoin

biological: Sargramostim

procedure: Therapeutic Conventional Surgery

drug: Thiotepa

drug: Topotecan Hydrochloride

drug: Vincristine Sulfate

drug: Melphalan Hydrochloride

drug: Lorlatinib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Ariel Fry Demetria

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