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CompletedNCT00005978Updated Oct 15, 2010

N99-01: Combination Chemotherapy, Radiation Therapy, and Stem Cell Transplantation in Treating Patients With Neuroblastoma

A Phase 1 interventional study of filgrastim and carboplatin in Neuroblastoma, sponsored by New Approaches to Neuroblastoma Therapy Consortium. Completed at 15 sites in United States. Open to participants aged 1 Year to 21 Years. Per ClinicalTrials.gov, last updated 2010-10-15.

Sponsored by New Approaches to Neuroblastoma Therapy Consortium · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Ages
1 Year to 21 Years
Sex
All
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Study summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different ways may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy.

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.

Read the detailed description

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.

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.

02

Conditions studied

  • Neuroblastoma

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Keywords

  • localized resectable neuroblastoma
  • regional neuroblastoma
  • disseminated neuroblastoma
  • stage 4S neuroblastoma
  • recurrent neuroblastoma
  • localized unresectable neuroblastoma
03

In context

Neuroblastoma

634 studies on the registry are indexed under Neuroblastoma; 122 are open to participants now.

Browse Neuroblastoma studies →

Lead sponsor

New Approaches to Neuroblastoma Therapy Consortium is the lead sponsor of 24 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
1 Year to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • 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
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Study design

Phase
Phase 1
Primary purpose
Treatment

Interventions

  • Biologicalfilgrastim
  • Procedureautologous bone marrow transplantation
  • Procedureperipheral blood stem cell transplantation
  • Radiationiobenguane I 131
  • Radiationradiation therapy
06

Study locations

15 sites
  • Children's Hospital Los Angeles
    Los Angeles, California 90027-0700, United States
  • Lucile Packard Children's Hospital at Stanford University Medical Center
    Palo Alto, California 94304, United States
  • UCSF Comprehensive Cancer Center
    San Francisco, California 94143, United States
  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
    Atlanta, Georgia 30322, United States
  • Children's Memorial Hospital - Chicago
    Chicago, Illinois 60614, United States
  • Indiana University Cancer Center
    Indianapolis, Indiana 46202-5289, United States
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
    Bethesda, Maryland 20892-1182, United States
  • Children's Hospital Boston
    Boston, Massachusetts 02115, United States
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • University of Michigan Comprehensive Cancer Center
    Ann Arbor, Michigan 48109-0914, United States
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229-3039, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Texas Children's Cancer Center
    Houston, Texas 77030-2399, United States
  • Children's Hospital and Regional Medical Center - Seattle
    Seattle, Washington 98105, United States
  • University of Wisconsin Comprehensive Cancer Center
    Madison, Wisconsin 53792-6164, United States
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References and documents

Publications

  • 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. PubMed 16421427 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 15, 2010, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00005978
Lead sponsor
New Approaches to Neuroblastoma Therapy Consortium
First posted
Dec 23, 2003
Start date
May 2000
Primary completion
Dec 2004
Last update
Oct 15, 2010

Study contacts

Katherine K. Matthay, MD
study chair · Children's Hospital Los Angeles

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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