N2001-02: I-MIBG With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine, may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as carboplatin, etoposide, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous peripheral stem cell or bone marrow transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 metaiodobenzylguanidine and combination chemotherapy with an autologous peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more tumor cells are killed. Giving radiation therapy after an autologous peripheral stem cell or bone marrow transplant may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving iodine I 131 metaiodobenzylguanidine together with combination chemotherapy and radiation therapy works in treating patients who are undergoing an autologous peripheral stem cell or bone marrow transplant for relapsed or refractory neuroblastoma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital Los Angeles
• Collaborator: National Cancer Institute (NCI)
• Treatments: 3-Iodobenzylguanidine; Carboplatin; Etoposide; Etoposide phosphate; Lenograstim; Melphalan

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed or refractory neuroblastoma

• Histologically confirmed and/or demonstration of tumor cells in bone marrow with elevated urinary catecholamine metabolites

• High-risk neuroblastoma must meet one of the following:

• Progressive disease prior to or after completion of induction therapy

• Mixed response or no response after completion of 4 courses of induction therapy

• Partial response after 4 courses of induction therapy allowed provided no prior participation in COG-A3973 or other phase III COG trials

• Measurable disease, defined as at least one metaiodobenzylguanidine (MIBG)-avid target lesion determined by diagnostic MIBG scan within 6 weeks of study entry (tumor sites that have received local irradiation within 3 months of study entry are not considered target lesions)

PATIENT CHARACTERISTICS:

Performance status

• Lansky 60-100% OR

• Karnofsky 60-100%

Life expectancy

• At least 2 months

Hematopoietic

• Hemoglobin ≥ 10 g/dL

• Absolute neutrophil count ≥ 750/mm^3

• Platelet count ≥ 50,000/mm^3 (if no marrow involvement by morphologic exam/no transfusion allowed) (> 20,000/mm^3 if metastatic tumor involvement of marrow by morphologic exam/transfusion allowed)

Hepatic

• Bilirubin < 1.3 mg/dL

• SGOT and SGPT < 5 times normal

• Hepatitis B surface antigen negative

• Hepatitis C negative

Renal

• Glomerular filtration rate or creatinine clearance ≥ 60 ml/min

• Creatinine ≤ 1.5 times normal for age as follows:

• 0.8 mg/dL (for patients ≤ 5 years of age)

• 1.0 mg/dL (for patients 6 to 10 years of age)

• 1.2 mg/dL (for patients 11 to 15 years of age)

• 1.5 mg/dL (for patients > 15 years of age)

Cardiovascular

• Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA OR

• Fractional shortening ≥ 27% by echocardiogram

Pulmonary

• Normal lung function defined as no dyspnea at rest and no oxygen requirement OR measured oxygen saturation > 93% on room air

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No disease of any major organ system that would preclude study compliance

• No concurrent hemodialysis

• No active infection requiring IV antivirals, antibiotics, or antifungals (patients on antifungal therapy are eligible provided they are culture- and biopsy-negative in suspected residual radiographic lesions)

• Patient weight within limits to receive ≤ maximum total allowable dose of ^131I-MIBG

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior myeloablative transplantation

• Prior submyeloablative transplantation allowed at discretion of principal investigator

• More than 3 weeks since prior biologic therapy

Chemotherapy

• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for mitomycin C or nitrosoureas)

• No prior melphalan therapy with a total dose of > 100 mg/m^2

Radiotherapy

• See Disease Characteristics

• At least 6 weeks since prior radiotherapy (6 months for craniospinal or whole lung radiotherapy)

• No prior total body irradiation

• No prior iodine I 131 MIBG (^131I-MIBG)

• No prior total abdominal or whole liver radiotherapy

• No prior local radiotherapy, including any of the following:

• 1200 cGy to more than 33% of both kidneys (patient must have at least one kidney that has not exceeded the dose/volume of radiation listed)

• 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver

Other

• Recovered from all prior therapy

• No medications with a potential interference of ^131I-MIBG uptake 1 week before and 2 weeks after completion of ^131I-MIBG