N99-01: Combination Chemotherapy, Radiation Therapy, and Stem Cell Transplantation in Treating Patients With Neuroblastoma
NCT ID: NCT00005978
Last Updated: 2010-10-15
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
INTERVENTIONAL
2000-05-31
Brief Summary
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PURPOSE: This phase I trial is studying the side effects and best dose of combination chemotherapy when given before stem cell transplant and radiation therapy in treating patients with neuroblastoma that has not responded to previous treatments.
Detailed Description
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* Determine the maximum tolerated dose and toxic effects of iodine I 131 metaiodobenzylguanidine (131 I-MIBG) plus ablative doses of carboplatin and etoposide administered with fixed-dose melphalan followed by autologous hematopoietic stem cell transplantation in patients with refractory or residual high-risk neuroblastoma.
* Determine the number of days until blood counts recover in these patients after receiving this treatment regimen.
* Determine the response rate to this treatment regimen in these patients.
* Determine the tumor dosimetry of 131 I-MIBG in patients with measurable soft tissue lesions.
OUTLINE: This is a dose-escalation study of iodine I 131 metaiodobenzylguanidine (131 I-MIBG), carboplatin, and etoposide. Patients are stratified according to glomerular filtration rate (at least 100 mL/min vs 60-99 mL/min).
Patients undergo peripheral blood stem cell harvest or bone marrow harvest at least 2 weeks prior to treatment with 131 I-MIBG.
Patients receive 131 I-MIBG IV over 120 minutes on day -21; melphalan IV on days -7 to -5; carboplatin and etoposide IV continuously over 96 hours on days -7 to -4; autologous hematopoietic stem cell transplantation IV over 15-30 minutes on day 0; and filgrastim (G-CSF) subcutaneously or IV starting on day 0 and continuing until blood counts recover. Radiotherapy is administered to the primary tumor site and metastatic sites twice daily for 7 consecutive days within 6 weeks of transplantation or once blood counts have recovered.
Cohorts of 3-6 patients receive escalating doses of 131 I-MIBG, carboplatin, and etoposide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Patients are followed at day 84, and then 2 months later if there is a complete response and/or partial response. Patients who continue therapy on other protocols are followed before starting the new therapy. All patients are followed for life for any delayed toxic effects related to study therapy, secondary malignancies, disease status, and survival.
PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per stratum) will be accrued for this study within 2-3 years.
Conditions
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Study Design
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TREATMENT
Interventions
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filgrastim
carboplatin
etoposide
melphalan
autologous bone marrow transplantation
peripheral blood stem cell transplantation
iobenguane I 131
radiation therapy
Eligibility Criteria
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Inclusion Criteria
* Diagnosis of neuroblastoma as evidenced by one of the following:
* Histological confirmation
* Demonstrates clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites
* High-risk refractory or residual disease
* Poorly responding disease, meeting 1 of the following criteria:
* Stable disease or partial response after at least 12 weeks of induction therapy
* Bone marrow containing greater than 100 tumor cells per 100,000 normal cells after 12 weeks of induction therapy
* Progressive disease during or after therapy
* At least 1 prior positive iodine I 131 metaiodobenzylguanidine (131 I-MIBG) scan since diagnosis and meets disease status criteria
PATIENT CHARACTERISTICS:
Age:
* 1 to 21 (1 to 20 at diagnosis)
Performance status:
* ECOG 0-2
Life expectancy:
* At least 2 months
Hematopoietic:
* Absolute neutrophil count at least 500/mm\^3
* Platelet count at least 20,000/mm\^3 (transfusion allowed)
* Hemoglobin at least 8 g/dL (transfusion allowed)
Hepatic:
* Bilirubin normal
* AST/ALT no greater than 3 times normal
* No active hepatitis (for HIV-positive patients only)
Renal:
* Glomerular filtration rate or creatinine clearance at least 60 mL/min
* Creatinine less than 1.5 times normal for age
Cardiovascular:
* Ejection fraction at least 55% OR
* Fractional shortening at least 30%
Pulmonary:
* No dyspnea at rest or exercise intolerance
* No requirement for supplemental oxygen
* No active pneumonia (for HIV-positive patients only)
Other:
* No disease of any major organ system that would preclude study participation
* No other active health problems (for HIV-positive patients only)
* No active infections requiring intravenous antivirals, antibiotics, or antifungals
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
* At least 3 weeks since prior biologic therapy and recovered
Chemotherapy:
* At least 3 weeks since prior chemotherapy and recovered
* No more than 100 mg/m\^2 total dose of prior melphalan
Endocrine therapy:
* Not specified
Radiotherapy:
* No prior total body, whole abdominal, or whole liver irradiation
* No prior therapy with 131 I-MIBG
* At least 2 weeks since prior radiotherapy (6 months for prior radiotherapy to craniospinal or whole lung fields or greater than 50% of bone marrow space) and recovered
Surgery:
* Prior surgical resection allowed
* Recovered from prior surgery
Other:
* No prior myeloablative therapy
* Prior submyeloablative therapy with peripheral blood stem cell support allowed
* No concurrent antiretrovirals for HIV-positive patients
* Concurrent prolonged antifungal allowed if culture and biopsy negative in suspected residual radiographic lesions
* No medications that may preclude uptake of 131 I-MIBG for 1 week prior and 2 weeks after administration of study drugs
* No concurrent hemodialysis
1 Year
21 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
New Approaches to Neuroblastoma Therapy Consortium
OTHER
Responsible Party
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UCSF
Principal Investigators
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Katherine K. Matthay, MD
Role: STUDY_CHAIR
Children's Hospital Los Angeles
Locations
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Children's Hospital Los Angeles
Los Angeles, California, United States
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States
UCSF Comprehensive Cancer Center
San Francisco, California, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Indiana University Cancer Center
Indianapolis, Indiana, United States
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States
Children's Hospital Boston
Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Texas Children's Cancer Center
Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States
Countries
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References
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Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JM. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006 Jan 20;24(3):500-6. doi: 10.1200/JCO.2005.03.6400.
Other Identifiers
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N99-01
Identifier Type: OTHER
Identifier Source: secondary_id
CDR0000067966
Identifier Type: -
Identifier Source: org_study_id