A COG Pilot Study of Intensive Induction Chemotherapy and 131I-MIBG/Irinotecan/Vincristine Followed by Myeloablative Busulfan-Melphalan (Bu-Mel) for Newly Diagnosed High-Risk Neuroblastoma
I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days to
30 years, with an induction block of meta-iodobenzylguanidine labeled with iodine-131
(131I-MIBG)/irinotecan/vincristine delivered after multi-agent chemotherapy, and
post-Induction busulfan/melphalan consolidation therapy.
I. To assess the tolerability of these regimens in these patients. II. To assess the
response rate of patients treated with these regimens. III. To describe the relationship of
tumor norepinephrine transporter (hNET) expression with radioiodinated MIBG uptake, at
diagnosis as well as with tumor response.
IV. To assess the relative reliability of 123 I-MIBG and 18FDG-PET imaging in assessment of
tumor activity at diagnosis, after 2 courses of induction chemotherapy, before surgical
resection and 131I-MIBG.
V. To compare detectable tumor burden before and immediate after therapy on the 123I-MIBG
VI. 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.
VII. To analyze busulfan first-dose pharmacokinetics as measured by area under the curve
(AUC) and to relate exposure to SOS incidence.
VIII. To describe the toxicity of 131I-MIBG combined with vincristine and irinotecan given
on a 5-day schedule.
OUTLINE: This is a pilot, multicenter study.
INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy.
Courses 1-2: Patients receive cyclophosphamide 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 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 (^131I-MIBG) induction therapy beginning 3-6 weeks after course 5. Patients
receive vincristine IV on day 0, irinotecan IV over 90 minutes on day 0-4, and 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 4-6 weeks after completion of induction therapy, patients
receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1.
Patients also complete a questionnaire regarding costs for travel and accommodations during
therapy. Blood samples maybe collected after the first dose of busulfan for pharmacokinetic
AUTOLOGOUS STEM CELL RESCUE: Patients undergo infusion of PBSC on day 0.
RADIOTHERAPY: Beginning 28-42 days after peripheral blood stem cell infusion, patients
undergo 12 fractions of external-beam radiotherapy (2D, 3D-conformal, or
intensity-modulated) to all areas of residual disease, primary tumor site, and involved
MAINTENANCE THERAPY: Beginning 66 days after transplantation, patients receive oral
isotretinoin twice daily 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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of MIBG avid patients who are able to be treated with 131I-MIBG/irinotecan/vincristine
This proportion will be calculated as the number of MIBG avid patients who receive 131I-MIBG/irinotecan/vincristine divided by the number of patients evaluable for the feasibility of MIBG endpoint. The definition of receive 131I-MIBG/irinotecan/vincristine is receiving 131I-MIBG infusion.
Up to 6 weeks after course 5 of induction
Children's Oncology Group
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|University of Alabama at Birmingham||Birmingham, Alabama 35294-3300|
|University of Texas Southwestern Medical Center||Dallas, Texas|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Children's Hospital Colorado||Aurora, Colorado 80045|
|University of California San Francisco Medical Center-Parnassus||San Francisco, California 94143|