Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma
Condition: Ganglioneuroblastoma; Stage 1 Neuroblastoma; Stage 2 Neuroblastoma; Stage 2A Neuroblastoma; Stage 2B Neuroblastoma; Stage 3 Neuroblastoma; Stage 4 Neuroblastoma; Stage 4S Neuroblastoma
MeSH terms: Neuroblastoma; Ganglioneuroblastoma
Intervention: Autologous Hematopoietic Stem Cell Transplantation; Busulfan; Cisplatin; Cyclophosphamide; Doxorubicin Hydrochloride; Etoposide; External Beam Radiation Therapy; Filgrastim; Laboratory Biomarker Analysis; Melphalan; Mesna; Peripheral Blood Stem Cell Transplantation; Pharmacological Study; Topotecan Hydrochloride; Vincristine Sulfate
Intervention description: Undergo autologous peripheral blood stem cell transplant; Given IV; Given IV; Given IV; Given IV; Given IV; Undergo EBRT; Given SC or IV; Optional correlative studies; Given IV; Given IV; Undergo autologous peripheral blood stem cell transplant; Correlative studies; Given IV; Given IV
Intervention MeSH terms: Cyclophosphamide; Melphalan; Busulfan; Mechlorethamine; Nitrogen Mustard Compounds; Cisplatin; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Etoposide phosphate; Topotecan; Podophyllotoxin; Lenograstim; Mesna
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 150.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No

Summary:

      This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after
      chemotherapy in treating patients with newly diagnosed neuroblastoma that is likely to come
      back or spread. Giving chemotherapy to the entire body before a stem cell transplant stops
      the growth of tumor cells by stopping them from dividing or killing them. After treatment,
      stem cells are collected from the patient's blood and stored. More chemotherapy or radiation
      therapy is 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
      chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a diagnosis of neuroblastoma (International Classification of
             Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma (nodular or
             intermixed) verified by histology or demonstration of clumps of tumor cells in bone
             marrow with elevated urinary catecholamine metabolites; patients with the following
             disease stages at diagnosis are eligible, if they meet the other specified criteria

          -  Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging
             System (INSS) stage 4 are eligible with the following:

               -  V-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN)
                  amplification (> 4-fold increase in MYCN signals as compared to reference
                  signals), regardless of age or additional biologic features or

               -  Age > 18 months (> 547 days) regardless of biologic features or

               -  Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic
                  features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid
                  [DNA] index = 1) or any biologic feature that is
                  indeterminate/unsatisfactory/unknown

          -  Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the
             following:

               -  MYCN amplification (> 4-fold increase in MYCN signals as compared to reference
                  signals), regardless of age or additional biologic features or

               -  Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN
                  status

          -  Patients with newly diagnosed neuroblastoma with INSS stage 2A/2B with MYCN
             amplification (> 4-fold increase in MYCN signals as compared to reference signals),
             regardless of age or additional biologic features

          -  Patients with newly diagnosed neuroblastoma with INSS stage 4S with MYCN amplification
             (> 4-fold increase in MYCN expression signals as compared to reference signals),
             regardless of additional biologic features

          -  Patients >= 365 days initially diagnosed with neuroblastoma INSS stage 1, 2, 4S who
             progressed to a stage 4 without interval chemotherapy; these patients must have been
             enrolled on ANBL00B1; study enrollment on ANBL12P1 must occur within 4 weeks of
             progression to stage 4 for INSS stage 1, 2, 4S

          -  Patients must not have had prior systemic therapy except for localized emergency
             radiation to sites of life-threatening or function-threatening disease and/or no more
             than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as
             per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification
             status and histology

          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
             mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

               -  Age 1 month to < 6 months: 0.4 mg/dL

               -  Age 6 months to < 1 year: 0.5 mg/dL

               -  Age 1 to < 2 years: 0.6 mg/dL

               -  Age 2 to < 6 years: 0.8 mg/dL

               -  Age 6 to < 10 years: 1 mg/dL

               -  Age 10 to < 13 years: 1.2 mg/dL

               -  Age 13 to < 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females)

               -  Age >= 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x
             ULN for age

          -  Shortening fraction of >= 27% by echocardiogram, or

          -  Ejection fraction of >= 50% by radionuclide evaluation

          -  No known contraindication to peripheral blood stem cell (PBSC) collection; examples of
             contraindications might be a weight or size less than that determined to be feasible
             at the collecting institution, or a physical condition that would limit the ability of
             the child to undergo apheresis catheter placement (if necessary) and/or the apheresis
             procedure

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met

        Exclusion Criteria:

          -  Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic
             features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not
             eligible

          -  Female patients who are pregnant are ineligible

          -  Lactating females are not eligible unless they have agreed not to breastfeed their
             infants

          -  Female patients of childbearing potential are not eligible unless a negative pregnancy
             test result has been obtained

          -  Sexually active patients of reproductive potential are not eligible unless they have
             agreed to use an effective contraceptive method for the duration of their study
             participation