This trial is active, not recruiting.

Conditions disseminated neuroblastoma, ganglioneuroblastoma, localized resectable neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma, stage 4s neuroblastoma
Treatments cyclophosphamide, topotecan hydrochloride, cisplatin, etoposide phosphate, vincristine sulfate, doxorubicin hydrochloride, iobenguane i 131, therapeutic conventional surgery, busulfan, melphalan, autologous hematopoietic stem cell transplantation, in vitro-treated peripheral blood stem cell transplantation, 3-dimensional conformal radiation therapy, external beam radiation therapy, intensity-modulated radiation therapy, isotretinoin, pharmacological study, questionnaire administration, laboratory biomarker analysis
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date October 2010
End date May 2016
Trial size 99 participants
Trial identifier NCT01175356, ANBL09P1, CDR0000682629, NCI-2011-01745, U10CA098543, U10CA180886


This clinical trial is studying induction therapy followed by meta-iodobenzylguanidine (MIBG) labeled with iodine-131 and chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma undergoing stem cell transplant, radiation therapy, and maintenance therapy with isotretinoin. Radioisotope therapy, such as MIBG labeled with iodine-131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as cisplatin, etoposide, busulfan, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant can replace blood-forming cells that are damaged by MIBG labeled with iodine-131 and chemotherapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
See Detailed Description.
cyclophosphamide CPM
Given IV
topotecan hydrochloride hycamptamine
Given IV
cisplatin CACP
Given IV
etoposide phosphate ETOP
Given IV
vincristine sulfate leurocristine sulfate
Given IV
doxorubicin hydrochloride ADM
Given IV
iobenguane i 131 131 I-MIBG
Given IV
therapeutic conventional surgery
Undergo surgery
busulfan BSF
Given IV
melphalan Alkeran
Given IV
autologous hematopoietic stem cell transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantation
in vitro-treated peripheral blood stem cell transplantation in vitro-treated PBPC transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantation
3-dimensional conformal radiation therapy 3D conformal radiation therapy
Undergo radiotherapy
external beam radiation therapy EBRT
Undergo radiotherapy
intensity-modulated radiation therapy IMRT
Undergo radiotherapy
isotretinoin 13-CRA
Given PO
pharmacological study pharmacological studies
Correlative studies
questionnaire administration
Ancillary studies
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Proportion of MIBG avid patients who are able to be treated with iobenguane I 131
time frame: Up to 6 weeks after course 5 of induction
Proportion of MIBG avid patients who are able to be treated with iobenguane I 131 and then Bu/Mel
time frame: Day -6 of conditioning
Percentage of average per capita income encompassed by the total of travel + housing + lost wages
time frame: Up to 10 years
Proportion of eligible high-risk patients accrued to the study
time frame: Up to 10 years
Event-free survival rate
time frame: Time from enrollment to the first occurrence of relapse, progression, secondary malignancy or death, assessed at 1 year

Secondary Outcomes

Response rate, defined as the proportion of evaluable patients who attain a response of partial response or better at the end of iobenguane I 131 + Bu/Mel therapy and local radiotherapy
time frame: Up to 10 years
Incidence of adverse events and SOS, assessed by Common Terminology Criteria version 4.0 for toxicity assessment and grading
time frame: Up to 10 years

Eligibility Criteria

Male or female participants from 1 year up to 30 years old.

Inclusion Criteria: - Patients have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria: - Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: - v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN) amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days regardless of additional biologic features - Age > 18 months (> 547 days) regardless of biologic features - Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminant/unsatisfactory/unknown - Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following: - MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), and age >= 365 days, regardless of additional biologic features - Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status - Patients with newly diagnosed INSS stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days, regardless of additional biologic features - Patients >= 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; it is to be noted that study enrollment must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S - Patients must have had no prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per low- or intermediate-risk neuroblastoma therapy (P9641, A3961, ANBL0531) prior to determination of MYCN amplification and histology - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR serum creatinine based on age and/or gender as follows: - 0.6 mg/dL (1 to < 2 years of age) - 0.8 mg/dL (2 to < 6 years of age) - 1.0 mg/dL (6 to < 10 years of age) - 1.2 mg/dL (10 to < 13 years of age) - 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age) - 1.7 mg/dL (male) or 1.4 mg/dL (female) ( >= 16 years of age) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age - Shortening fraction >= 27% by echocardiogram or - Ejection fraction >= 50% by radionuclide evaluation - 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 - All patients and/or their parents or legal guardians must sign a written informed consent - All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: - Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method - Female patients who are lactating must agree to stop breast-feeding - Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1) are not eligible - Patients are not eligible if they have received local radiation which includes any of the following: 1200 centigray (cGy) to more than 33% of both kidneys (patient must have at least 1 kidney that has not exceeded the dose/volume of radiation listed) or 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver; emergency local irradiation is allowed prior to study entry, provided the patient still meets eligibility criteria

Additional Information

Official title A COG Pilot Study of Intensive Induction Chemotherapy and 131I-MIBG Followed by Myeloablative Busulfan/Melphalan (Bu/Mel) for Newly Diagnosed High-Risk Neuroblastoma
Principal investigator Brian Weiss, MD
Description PRIMARY OBJECTIVE: I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of meta-iodobenzylguanidine labeled with iodine-131 (131I-MIBG [iobenguane I 131]) delivered after multi-agent chemotherapy, and b) post-induction busulfan/melphalan (Bu/Mel) consolidation therapy. SECONDARY OBJECTIVES: I. To assess the tolerability of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of 131I-MIBG therapy delivered after multi-agent chemotherapy, and b) the tolerability of receiving post-induction Bu/Mel consolidation therapy with autologous stem-cell rescue (ASCR), and local radiation therapy. TERTIARY OBJECTIVES: I. To assess the response rate after a regimen of induction chemotherapy and 131I-MIBG and after a consolidation regimen of Bu/Mel with ASCR and local radiation therapy. II. To describe the relationship of tumor norepinephrine transporter (hNET) expression with radioiodinated MIBG uptake, at diagnosis as well as with tumor response. III. To assess the relative reliability of 123 I-MIBG and fludeoxyglucose F-18 (18FDG)-positron emission tomography (PET) imaging in assessment of tumor activity at diagnosis, and prior to surgical resection. IV. To compare detectable tumor burden on the pre-surgical resection radioiodinated-MIBG diagnostic scan and the immediate post-MIBG therapy 131I-MIBG scan. V. To test for the relationship of occurrence of sinusoidal obstruction syndrome (SOS) to Bu/Mel or to whole-body radiation dose or delayed radiation clearance due to 131I-MIBG. VI. To analyze busulfan pharmacokinetics as measured by area under the curve (AUC) and relate exposure to SOS incidence. OUTLINE: INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy. Courses 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Patients undergo peripheral blood stem cell (PBSC) collection after course 2. Course 3 and 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3. Patients undergo surgery to remove remaining tumor following course 5. Course 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2 and vincristine sulfate IV over 1 minute and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Patients without progressive disease proceed to iobenguane I 131 induction therapy beginning 3-6 weeks after course 5. Patients receive iobenguane I 131 IV over 90-120 minutes on day 1. SURGERY: Patients undergo surgery after course 4 or before consolidation therapy. CONSOLIDATION THERAPY: Within 10-12 weeks from the date of iobenguane I 131 infusion, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1. AUTOLOGOUS STEM CELL RESCUE: Patients undergo infusion of PBSC on day 0. RADIOTHERAPY: Beginning no sooner than 42 days after peripheral blood stem cell infusion, patients undergo 12 fractions of external-beam radiotherapy (2 dimensional [D], 3D-conformal, or intensity-modulated) to all areas of residual disease, primary tumor site, and involved nodal disease. MAINTENANCE THERAPY: Beginning 66 days after transplantation, patients receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for 6 courses. After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Children's Oncology Group.
Location data was received from the National Cancer Institute and was last updated in July 2016.