Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma
Condition: Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Recurrent Neuroblastoma; Regional Neuroblastoma; Stage 4 Neuroblastoma; Stage 4S Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: Autologous Hematopoietic Stem Cell Transplantation; Carboplatin; Cisplatin; Cyclophosphamide; Doxorubicin Hydrochloride; Etoposide; External Beam Radiation Therapy; Filgrastim; Isotretinoin; Laboratory Biomarker Analysis; Melphalan; Peripheral Blood Stem Cell Transplantation; Pharmacological Study; Thiotepa; Topotecan Hydrochloride; Vincristine Sulfate Liposome
Intervention description: Undergo autologous peripheral blood stem cell transplant; Given IV; Given IV; Given IV; Given IV; Given IV; Undergo EBRT; Given IV or SC; Given orally; Correlative studies; Given IV; Undergo autologous peripheral blood stem cell transplant; Correlative studies; Given IV; Given IV; Given IV
Intervention MeSH terms: Vitamin A; Cyclophosphamide; Melphalan; Mechlorethamine; Thiotepa; Nitrogen Mustard Compounds; Cisplatin; Carboplatin; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Etoposide phosphate; Topotecan; Tretinoin; Podophyllotoxin; Isotretinoin; Lenograstim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 665.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial compares two different high-dose chemotherapy regimens
      followed by a stem cell transplant in treating younger patients with high-risk neuroblastoma.
      Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either
      by killing the cells or by stopping them from dividing. Giving combination chemotherapy
      before surgery may make the tumor smaller and reduce the amount of normal tissue that needs
      to be removed. Giving these treatments before a peripheral blood stem cell transplant helps
      kill any tumor cells that are in the body and helps make room in the patient?s bone marrow
      for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected
      from the patient's blood and stored. High-dose chemotherapy and radiation therapy is then
      given to prepare the bone marrow for the stem cell transplant. The stem cells are then
      returned to the patient to replace the blood-forming cells that were destroyed by the high-
      chemotherapy. It is not yet known which regimen of high-dose chemotherapy is more effective
      for patients with high-risk neuroblastoma undergoing a peripheral blood stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of neuroblastoma or ganglioneuroblastoma by histology or as evidenced by the
             presence of clumps of tumor cells in bone marrow and elevated catecholamine
             metabolites in urine meeting any of the following criteria:

               -  Patients with newly diagnosed neuroblastoma with International Neuroblastoma
                  Staging System (INSS) stage 4 disease are eligible with the following:

                    -  MYCN amplification (i.e., greater than four-fold increase in MYCN signals as
                       compared to reference signals), regardless of age or additional biologic
                       features

                    -  Age > 18 months (i.e., > 547 days) regardless of biologic features

                    -  Age 12-18 months (i.e., 365-547 days) with none of the following three
                       favorable biologic features (i.e., non-amplified MYCN, favorable pathology,
                       and deoxyribonucleic acid [DNA] index > 1)

               -  Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with
                  the following:

                    -  MYCN amplification (i.e., greater than four-fold increase in MYCN signals as
                       compared to reference signals), regardless of age or additional biologic
                       features

                    -  Age > 18 months (i.e., > 547 days) with unfavorable pathology, regardless of
                       MYCN status

               -  Patients with newly diagnosed INSS stage 2a or 2b with MYCN amplification (i.e.,
                  greater than four-fold increase in MYCN signals as compared to reference
                  signals), regardless of age or additional biologic features

               -  Patients with newly diagnosed INSS stage 4s with MYCN amplification (i.e.,
                  greater than four-fold increase in MYCN signals as compared to reference
                  signals), regardless of additional biologic features

               -  Patients >= 365 days initially diagnosed with INSS stage 1, 2, or 4S and who
                  progressed to a stage 4 without interval chemotherapy

                    -  Must have been enrolled on COG-ANBL00B1

          -  Creatinine clearance or radioisotope glomerular filtration rate ? 70mL/min OR serum
             creatinine based on age/gender as follows:

               -  1 month to < 6 months: 0.4 mg/dL

               -  6 months to < 1 year: 0.5 mg/dL

               -  1 to < 2 years: 0.6 mg/dL

               -  2 to < 6 years: 0.8 mg/dL

               -  6 to < 10 years: 1 mg/dL

               -  10 to < 13 years: 1.2 mg/dL

               -  10 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)

               -  >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)

          -  Total bilirubin ? 1.5 times upper limit of normal (ULN) for age

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 10 times ULN for
             age

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Shortening fraction >= 27% by echocardiogram (ECHO) OR left ventricular ejection
             fraction (LVEF) >= 50% by radionuclide angiogram

          -  No known contraindication (e.g., size, weight or physical condition) to peripheral
             blood stem cell collection

          -  No prior systemic therapy except for localized emergency radiation to sites of
             life-threatening or function-threatening disease

          -  No more than one course of chemotherapy per low- or intermediate-risk neuroblastoma
             therapy prior to determination of MYCN amplification and histology