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Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)
Not Recruiting
Trial ID: NCT03126916
Purpose
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)
Eligibility
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
Intervention(s):
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
afrydeme@stanford.edu