Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People with 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.
Neuroblastoma (Pediatrics)
Pediatrics
Phase III
Both
Chemotherapy - cytotoxic
Supportive Care
Busulfan
Carboplatin
Cisplatin
Crizotinib
Cyclophosphamide (CPM)
Cyclophosphamide (CTX)
Dexrazoxane
Doxorubicin
Etoposide
Filgrastim (GCSF)
I-MIBG
Interleukin (IL-2, Aldesleukin)
Isotretinoin
Melphalan
Mesna
PF-02341066
Pegfilgrastim
Potassium Iodide
Sargramostim
Thiotepa
Topotecan
Unituxin (Dinutuximab)
Vincristine
Benedetti, Daniel
National
Vanderbilt University
09-17-2018
Treatment
COGANBL1531
NCT03126916
Eligibility
365 Days
BOTH
NO
Inclusion Criteria:
Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
Patient must be >= 365 days and =
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 = 16 years: male = 1.7; female = 1.4
Total bilirubin =
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT])
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
Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
Patient must be >= 365 days and =
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 = 16 years: male = 1.7; female = 1.4
Total bilirubin =
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT])
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
