RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy given before surgery followed by peripheral stem cell or bone marrow transplantation in treating infants who have newly diagnosed neuroblastoma.

Condition	Treatment or Intervention	Phase
localized resectable neuroblastoma regional neuroblastoma disseminated neuroblastoma stage 4S neuroblastoma localized unresectable neuroblastoma	Drug: busulfan  Drug: carboplatin  Drug: cyclophosphamide  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: melphalan  Drug: vincristine  Procedure: autologous bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: conventional surgery  Procedure: cytokine therapy  Procedure: peripheral blood stem cell transplantation  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the survival of infants with newly diagnosed stage II, III, IV, or IVS neuroblastoma with MYCN amplification treated with etoposide, carboplatin, cyclophosphamide, doxorubicin, and vincristine followed by surgery and busulfan and melphalan with autologous peripheral blood stem cell or bone marrow transplantation.
• Determine whether there are prognostic criteria that could be used in future therapeutic stratification of these patients.

OUTLINE: This is a multicenter study.

Patients receive VP-CARBO chemotherapy comprising etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses. Patients then receive CADO chemotherapy comprising cyclophosphamide IV over 1 hour on days 1-5, doxorubicin IV over 6 hours on days 4 and 5, and vincristine IV on days 1 and 5. Treatment repeats every 21 days for 2 courses.

Patients receive filgrastim (G-CSF) subcutaneously daily for 5 days. Patients undergo leukapheresis to collect peripheral blood stem cells (PBSC). Patients who do not mobilize sufficient cells undergo bone marrow harvest.

Patients eligible for surgery undergo surgical resection. Patients with stage IV disease with less than complete response of metastatic disease after initial chemotherapy are removed from the study.

Beginning within 2 weeks after surgery, patients receive 1 additional course of VP-CARBO chemotherapy followed by 1 additional course of CADO chemotherapy.

After at least 3 weeks, patients receive high-dose chemotherapy comprising busulfan IV over 24 hours on days -7 to -3 and melphalan IV on day -2. PBSC or bone marrow are reinfused on day 0.

At least 2 months after the completion of high-dose chemotherapy and bone marrow or PBSC transplantation, patients undergo radiotherapy to the primary site, according to preoperative imaging studies. Patients are treated with oral tretinoin after megatherapy.

Patients are followed within 6 months and then annually for 5 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.

Ages Eligible for Study:  up to  1 Year,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed stage II, III, IV, or IVS neuroblastoma or ganglioneuroblastoma
• MYCN amplification (i.e., at least 10 copies)

PATIENT CHARACTERISTICS: Age:

• Under 12 months at diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Austria
      St. Anna Children's Hospital, Vienna,  A-1090,  Austria; Recruiting
Belgium
      Universitair Ziekenhuis Gent, Ghent,  B-9000,  Belgium; Recruiting
Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark; Recruiting
France
      Centre Hospitalier Regional de Purpan, Toulouse,  31026,  France; Recruiting
Italy
      Istituto Giannina Gaslini, Genoa,  16148,  Italy; Recruiting
Norway
      Rikshospitalet University Hospital, Oslo,  0027,  Norway; Recruiting
Portugal
      Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A., Lisboa,  1099-023 Codex,  Portugal; Recruiting
Spain
      Hospital Universitario LA FE, Valencia,  46009,  Spain; Recruiting
Sweden
      Ostra Sjukhuset, GOTHENBURG,  41685,  Sweden; Recruiting
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland; Recruiting
United Kingdom, England
      Bristol Royal Hospital for Children, Bristol,  England,  BS2 8BJ,  United Kingdom; Recruiting

Study chairs or principal investigators

Adela Canete, MD,  Study Chair,  Hospital Universitario LA FE   

Study ID Numbers:  CDR0000068982; EURO-INF-NB-STUDY-1999-99.4; EU-20125D; NCT00025649
Record last reviewed:  June 2002
Last Updated:  January 6, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025649
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08