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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by Children's Oncology Group
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group Identifier:
First received: August 3, 2010
Last updated: September 11, 2015
Last verified: September 2015
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.

Condition Intervention
Disseminated Neuroblastoma
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Regional Neuroblastoma
Stage 4S Neuroblastoma
Drug: cyclophosphamide
Drug: topotecan hydrochloride
Drug: cisplatin
Drug: etoposide phosphate
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Radiation: iobenguane I 131
Procedure: therapeutic conventional surgery
Drug: busulfan
Drug: melphalan
Procedure: autologous hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Radiation: 3-dimensional conformal radiation therapy
Radiation: external beam radiation therapy
Radiation: intensity-modulated radiation therapy
Drug: isotretinoin
Other: pharmacological study
Other: questionnaire administration
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    This proportion will be calculated as the number of MIBG avid patients who receive iobenguane I 131 divided by the number of patients evaluable for the feasibility of MIBG endpoint. The definition of receive iobenguane I 131 is receiving iobenguane I 131.

  • 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 ] [ Designated as safety issue: No ]
    This proportion will be calculated as the number of MIBG avid patients who receive iobenguane I 131 and Bu/Mel divided by the number of patients evaluable for the feasibility of MIBG and Bu/Mel consolidation endpoint. The definition of receiving Bu/Mel conditioning is receiving the first dose of planned Busulfan on 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 ] [ Designated as safety issue: No ]
    Patient/caregiver surveys will provide the information about travel for each patient. Cost of travel for each person will be determined using standard mileage reimbursement rates. Standard federal per diem rates will be utilized for families who stay in a hotel. Lost wages will be calculated for up to a maximum of 2 adults. In order to determine if the 'out-of-pocket' costs are less than 10% of yearly income, expenditures will be totaled and compared to the average per capita income, assuming 52-weeks with a 40-hour work week.

  • Proportion of eligible high-risk patients accrued to the study [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Event-free survival rate [ Time Frame: Time from enrollment to the first occurrence of relapse, progression, secondary malignancy or death, assessed at 1 year ] [ Designated as safety issue: No ]
    A 95% confidence interval will be calculated for the 1-year EFS rate. Will perform a comparison of the 1-year EFS rate on this study versus a hypothesized model of the standard using the methodology of Woolson.

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Response will be determined using the International Response Criteria.

  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 105
Study Start Date: October 2010
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide phosphate
Given IV
Other Names:
  • ETOP
  • Etopophos
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Radiation: iobenguane I 131
Given IV
Other Names:
  • 131 I-MIBG
  • I 131 Metaiodobenzylguanidine
  • Iodine I 131 Metaiodobenzylguanidine
Procedure: therapeutic conventional surgery
Undergo surgery
Drug: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantation
Other Names:
  • in vitro-treated PBPC transplantation
  • in vitro-treated PBSC
  • in vitro-treated peripheral blood progenitor cell transplantation
  • PBPC transplantation, in vitro-treated
  • peripheral blood progenitor cell transplantation, in vitro-treated
Radiation: 3-dimensional conformal radiation therapy
Undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: external beam radiation therapy
Undergo radiotherapy
Other Name: EBRT
Radiation: intensity-modulated radiation therapy
Undergo radiotherapy
Other Name: IMRT
Drug: isotretinoin
Given PO
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description


Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01175356

  Hide Study Locations
United States, Alabama
Children's Hospital of Alabama Recruiting
Birmingham, Alabama, United States, 35233
Contact: Alyssa T. Reddy    205-934-0309      
Principal Investigator: Alyssa T. Reddy         
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Alyssa T. Reddy    205-934-0309      
Principal Investigator: Alyssa T. Reddy         
United States, Arizona
Phoenix Childrens Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Jessica Boklan    602-546-0920      
Principal Investigator: Jessica Boklan         
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Leo Mascarenhas    323-361-4110      
Principal Investigator: Leo Mascarenhas         
University of California San Francisco Medical Center-Parnassus Recruiting
San Francisco, California, United States, 94143
Contact: Katherine K. Matthay    877-827-3222      
Principal Investigator: Katherine K. Matthay         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Timothy P. Garrington    720-777-6672      
Principal Investigator: Timothy P. Garrington         
United States, Connecticut
Connecticut Children's Medical Center Recruiting
Hartford, Connecticut, United States, 06106
Contact: Michael S. Isakoff    860-545-9981      
Principal Investigator: Michael S. Isakoff         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Jeffrey S. Dome    202-884-2549      
Principal Investigator: Jeffrey S. Dome         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Susan L. Cohn    773-834-7424      
Principal Investigator: Susan L. Cohn         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Carlos Rodriguez-Galindo    866-790-4500      
Principal Investigator: Carlos Rodriguez-Galindo         
United States, Michigan
C S Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Rajen Mody    800-865-1125      
Principal Investigator: Rajen Mody         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Stuart H. Gold    877-668-0683   
Principal Investigator: Stuart H. Gold         
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Susan G. Kreissman    888-275-3853      
Principal Investigator: Susan G. Kreissman         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Brian D. Weiss    513-636-2799      
Principal Investigator: Brian D. Weiss         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Yael P. Mosse    215-590-2810      
Principal Investigator: Yael P. Mosse         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Jacqueline M. Kraveka    843-792-9321      
Principal Investigator: Jacqueline M. Kraveka         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Naomi J. Winick    214-648-7097      
Principal Investigator: Naomi J. Winick         
Cook Children's Medical Center Terminated
Fort Worth, Texas, United States, 76104
United States, Utah
Primary Children's Hospital Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Phillip E. Barnette    801-585-5270      
Principal Investigator: Phillip E. Barnette         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Douglas S. Hawkins    866-987-2000      
Principal Investigator: Douglas S. Hawkins         
Providence Sacred Heart Medical Center and Children's Hospital Recruiting
Spokane, Washington, United States, 99204
Contact: Judy L. Felgenhauer    800-228-6618   
Principal Investigator: Judy L. Felgenhauer         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Kenneth B. DeSantes    608-262-5223      
Principal Investigator: Kenneth B. DeSantes         
Midwest Children's Cancer Center Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Meghen B. Browning    414-805-4380      
Principal Investigator: Meghen B. Browning         
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Brian Weiss, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group Identifier: NCT01175356     History of Changes
Other Study ID Numbers: ANBL09P1, NCI-2011-01745, CDR0000682629, ANBL09P1, ANBL09P1, U10CA180886, U10CA098543
Study First Received: August 3, 2010
Last Updated: September 11, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Etoposide phosphate
Liposomal doxorubicin
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Dermatologic Agents
Diagnostic Uses of Chemicals
Enzyme Inhibitors processed this record on November 25, 2015