Clinical Trial: 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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 sy
Sponsor: Children's Oncology Group

Current Primary Outcome:

  • 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 ]
    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 ]
    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 ]
    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 [&nbs

    Original Primary Outcome:

    • Proportion of patients treated with 131 I-MIBG, carboplatin, etoposide, and melphalan
    • 1-year event-free survival rate


    Current Secondary Outcome:

    • 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 ]
      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 ]


    Original Secondary Outcome:

    • Response rate
    • Tumor burden
    • Toxicity
    • Relationship of SOS to dosages of myeloablative consolidation therapy and ASCR, and whole-body radiation or delay of radiation clearance due to 131 I-MIBG


    Information By: Children's Oncology Group

    Dates:
    Date Received: August 3, 2010
    Date Started: October 2010
    Date Completion:
    Last Updated: February 7, 2017
    Last Verified: February 2017