A COG Pilot Study of Intensive Induction Chemotherapy and 131I-MIBG Followed by Myeloablative Busulfan/Melphalan (Bu/Mel) for Newly Diagnosed High-Risk Neuroblastoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Children's Oncology Group
- Enrollment
- 99
- Locations
- 25
- Primary Endpoint
- Percentage of MIBG Avid Patients Treated With MIBG Labeled With Iodine-131 and Bu/Mel Chemotherapy
Study Overview
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.
Detailed 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:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 30 Years (Child, Adult)
- Sex
- All
- 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
Arms & Interventions
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Isotretinoin (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Laboratory Biomarker Analysis (Other)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Pharmacological Study (Other)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Questionnaire Administration (Other)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Therapeutic Conventional Surgery (Procedure)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Melphalan (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: In Vitro-Treated Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Intensity-Modulated Radiation Therapy (Radiation)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Iobenguane I-131 (Radiation)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: 3-Dimensional Conformal Radiation Therapy (Radiation)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Busulfan (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Cisplatin (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Cyclophosphamide (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Doxorubicin Hydrochloride (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Etoposide Phosphate (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: External Beam Radiation Therapy (Radiation)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Topotecan Hydrochloride (Drug)
Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Intervention: Vincristine Sulfate (Drug)
Outcomes
Primary Outcomes
Percentage of MIBG Avid Patients Treated With MIBG Labeled With Iodine-131 and Bu/Mel Chemotherapy
Time Frame: Up to day -6 of conditioning
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%.
Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131
Time Frame: Up to 6 weeks after course 5 of induction
Number of MIBG avid patients who receive 131I-MIBG divided by the number of patients evaluable for the feasibility of MIBG endpoint x 100%.
Secondary Outcomes
- 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)