Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin

NCT01175356 | Completed Phase 1 Results DMC

• 5 other identifiers: ANBL09P1NCI-2011-01745CDR0000682629U10CA098543U10CA180886
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 25

Brief Summary

This pilot clinical trial studies induction therapy followed by iobenguane I 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 iobenguane I 131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as carboplatin, etoposide phosphate, 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 may be able to replace blood-forming cells that are destroyed by iobenguane I 131 and chemotherapy. Giving radioisotope therapy, chemotherapy, and peripheral stem cell transplant may kill more tumor cells.

Conditions

Ganglioneuroblastoma; Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Regional Neuroblastoma; Stage 4 Neuroblastoma; Stage 4S Neuroblastoma

Outcome Measures

Primary Outcomes (2)

• Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131

  Number of MIBG avid patients who receive 131I-MIBG divided by the number of patients evaluable for the feasibility of MIBG endpoint x 100%.

  Up to 6 weeks after course 5 of induction

• Percentage of MIBG Avid Patients Treated With MIBG Labeled With Iodine-131 and Bu/Mel Chemotherapy

  Number of MIBG avid patients who receive 131I-MIBG and Bu/Mel divided by the number of patients evaluable for the feasibility of MIBG and Bu/Mel consolidation endpoint x 100%.

  Up to day -6 of conditioning

Secondary Outcomes (1)

• Incidence of Unacceptable Toxicity and Sinusoidal Obstruction Syndrome (SOS), Assessed by Common Terminology Criteria (CTV)v.4.0 for Toxicity Assessment and Grading for I-MIBG

  Up to 6 weeks after course 5 of induction

Study Arms (1)

Treatment (131I-MIBG, chemotherapy)

EXPERIMENTAL

See Detailed Description.

Radiation: 3-Dimensional Conformal Radiation Therapy; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Etoposide Phosphate; Radiation: External Beam Radiation Therapy; Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation; Radiation: Intensity-Modulated Radiation Therapy; Radiation: Iobenguane I-131; Drug: Isotretinoin; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Other: Pharmacological Study; Other: Questionnaire Administration; Procedure: Therapeutic Conventional Surgery; Drug: Topotecan Hydrochloride; Drug: Vincristine Sulfate

Interventions

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (131I-MIBG, chemotherapy)

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo radiotherapy

Also known as: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D radiotherapy, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy, Radiation, 3D Conformal, Three dimensional external beam radiation therapy (procedure)

Treatment (131I-MIBG, chemotherapy)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous in vitro-treated peripheral blood stem cell transplantation

Also known as: AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant, Autologous Stem Cell Transplantation, Stem Cell Transplantation, Autologous

Treatment (131I-MIBG, chemotherapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (131I-MIBG, chemotherapy)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (131I-MIBG, chemotherapy)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

Treatment (131I-MIBG, chemotherapy)

Etoposide Phosphate DRUG

Given IV

Also known as: Etopophos

Treatment (131I-MIBG, chemotherapy)

External Beam Radiation Therapy RADIATION

Undergo radiotherapy

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Treatment (131I-MIBG, chemotherapy)

In Vitro-Treated Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous in vitro-treated peripheral blood stem cell transplantation

Also known as: in vitro-treated PBPC transplantation, in vitro-treated peripheral blood progenitor cell transplantation

Treatment (131I-MIBG, chemotherapy)

Intensity-Modulated Radiation Therapy RADIATION

Undergo radiotherapy

Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Treatment (131I-MIBG, chemotherapy)

Iobenguane I-131 RADIATION

Given IV

Also known as: (131)I-MIBG, 131I-MIBG, I 131 Meta-iodobenzylguanidine, I-131 Metaiodobenzylguanidine, Iobenguane (131I), Iobenguane I 131, Iodine I 131 Metaiodobenzylguanidine, MIBG I-131, Raiatt MIBG-I 131

Treatment (131I-MIBG, chemotherapy)

Isotretinoin DRUG

Given PO

Also known as: 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid, 13-cRA, Absorica, Accure, Accutane, Amnesteem, cis-Retinoic Acid, Cistane, Claravis, Isotretinoinum, Isotrex, Isotrexin, Myorisan, Neovitamin A, Neovitamin A Acid, Oratane, Retinoicacid-13-cis, Ro 4-3780, Ro-4-3780, Roaccutan, Roaccutane, Roacutan, Sotret, ZENATANE

Treatment (131I-MIBG, chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (131I-MIBG, chemotherapy)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalan for Injection-Hepatic Delivery System, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (131I-MIBG, chemotherapy)

Pharmacological Study OTHER

Correlative studies

Treatment (131I-MIBG, chemotherapy)

Questionnaire Administration OTHER

Ancillary studies

Treatment (131I-MIBG, chemotherapy)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (131I-MIBG, chemotherapy)

Topotecan Hydrochloride DRUG

Given IV

Also known as: Evotopin, Hycamptamine, Hycamtin, Nogitecan Hydrochloride, Potactasol, SKF S 104864 A, SKF S-104864-A, SKF S104864A, Topotec, Topotecan HCl, topotecan hydrochloride (oral)

Treatment (131I-MIBG, chemotherapy)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Treatment (131I-MIBG, chemotherapy)

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (25)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Weiss BD, Yanik G, Naranjo A, Zhang FF, Fitzgerald W, Shulkin BL, Parisi MT, Russell H, Grupp S, Pater L, Mattei P, Mosse Y, Lai HA, Jarzembowski JA, Shimada H, Villablanca JG, Giller R, Bagatell R, Park JR, Matthay KK. A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study. Pediatr Blood Cancer. 2021 Oct;68(10):e29117. doi: 10.1002/pbc.29117. Epub 2021 May 24.

  PMID: 34028986 DERIVED

MeSH Terms

Conditions

Ganglioneuroblastoma; Neuroblastoma

Interventions

Radiotherapy, Conformal; Stem Cell Transplantation; Busulfan; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Cyclophosphamide; Doxorubicin; etoposide phosphate; Congresses as Topic; Radiation; Radiotherapy, Intensity-Modulated; 3-Iodobenzylguanidine; Isotretinoin; Melphalan; Topotecan; Vincristine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Organizations; Health Care Economics and Organizations; Physical Phenomena; Guanidines; Amidines; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Iodinated; Retinoids; Carotenoids; Polyenes; Alkenes; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Biological Factors; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Brian D Weiss

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 4, 2010
• Study Start: December 21, 2011
• Primary Completion: September 28, 2016
• Study Completion: December 31, 2025
• Last Updated: January 23, 2026
• Results First Posted: September 28, 2017

Record last verified: 2026-01

Locations

US (25)