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Phase I Study of Iodine I 131 Metaiodobenzylguanidine Plus Intensive Chemotherapy Followed By Autologous Hematopoietic Stem Cell Transplantation in Patients With Refractory or Residual High-Risk Neuroblastoma
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Trial Contact Information Registry Information
Alternate Title
Combination Chemotherapy, Radiation Therapy, and Stem Cell Transplantation in Treating Patients With Neuroblastoma
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase I | Treatment | Closed | 1 to 21 (1 to 20 at diagnosis) | NANT-99-01 CHLA-LA-NANT-99-01, NCI-V00-1592, NCT00005978 |
Objectives - 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.
Entry Criteria Disease Characteristics:
- Diagnosis of neuroblastoma as evidenced by one of the following:
- Histological confimation
- 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
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/m2 total dose of prior melphalan
Endocrine therapy: 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
Patient Characteristics:
Age: - 1 to 21 (1 to 20 at diagnosis)
Performance status: Life expectancy: Hematopoietic: - Absolute neutrophil count at least 500/mm3
- Platelet count at least 20,000/mm3 (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
Expected Enrollment A total of 30-60 patients (15-30 per stratum) will be accrued for this study
within 2-3 years. 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. Published ResultsMatthay KK, Tan JC, Villablanca JG, et al.: 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 24 (3): 500-6, 2006.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations New Approaches to Neuroblastoma Therapy Consortium | | | Katherine Matthay, MD, Protocol chair | | | |
Registry Information | | Official Title | | Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study | | Trial Start Date | | 2000-05-17 | | Registered in ClinicalTrials.gov | | NCT00005978 | | Date Submitted to PDQ | | 2000-05-11 | | Information Last Verified | | 2005-02-09 | | NCI Grant/Contract Number | | CA81403 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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