Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma
Condition: Ganglioneuroblastoma; High Risk Neuroblastoma
MeSH terms: Neuroblastoma; Ganglioneuroblastoma
Intervention: Autologous Hematopoietic Stem Cell Transplantation; Carboplatin; Cisplatin; Cyclophosphamide; Dexrazoxane; Dinutuximab; Doxorubicin; Etoposide; External Beam Radiation Therapy; Isotretinoin; Melphalan; Sargramostim; Thiotepa; Topotecan; Vincristine
Intervention description: Undergo ASCT; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Undergo EBRT; Given PO; Given IV; Given SC; 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; Daunorubicin; Topotecan; Tretinoin; Podophyllotoxin; Dinutuximab; Dexrazoxane; Razoxane; 3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione; Isotretinoin; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No

Summary:

      This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim
      work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy
      with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune
      system and may interfere with the ability of tumor cells to grow and spread. Sargramostim
      helps the body produce normal infection-fighting white blood cells. These cells also help the
      dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such
      as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan,
      etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the
      body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells).
      Giving dinutuximab and sargramostim with combination chemotherapy may work better than
      combination chemotherapy alone in treating patients with high-risk neuroblastoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P1.

          -  Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular)
             verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone
             marrow with elevated urinary catecholamine metabolites. The following disease groups
             are eligible:

               -  Patients with International Neuroblastoma Risk Group (INRG) stage M disease are
                  eligible if found to have either of the following features:

                    -  MYCN amplification (> 4-fold increase in MYCN signals as compared to
                       reference signals), regardless of age or additional biologic features; OR

                    -  Age > 547 days regardless of biologic features;

               -  Patients with INRG stage MS disease with MYCN amplification

               -  Patients with INRG stage L2 disease with MYCN amplification

               -  Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS
                  disease who progress to stage M without prior chemotherapy may enroll within 4
                  weeks of progression to stage M.

               -  Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1
                  disease who progress to stage M without systemic therapy may enroll within 4
                  weeks of progression to stage M.

          -  Patients initially recognized to have high-risk disease must have had no prior
             systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis
             and within allowed timing as described).

          -  Patients observed or treated with a single cycle of chemotherapy per a low or
             intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar)
             for what initially appeared to be non-high risk disease but subsequently found to meet
             the criteria will also be eligible.

          -  Patients who receive localized emergency radiation to sites of life-threatening or
             function-threatening disease prior to or immediately after establishment of the
             definitive diagnosis will be eligible.

          -  Creatinine clearance (CrCl) or radioisotope glomerular filtration rate (GFR) >= 70
             mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:

               -  Age 1 month to < 6 months (male 0.4 mg/dL, female 0.4 mg/dL)

               -  Age 6 months to < 1 year (male 0.5 mg/dL, female 0.5 mg/dL)

               -  Age 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)

               -  Age 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)

               -  Age 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)

               -  Age 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)

               -  Age 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)

               -  Age >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to
                  enrollment).

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
             enrollment).

          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x
             ULN. For the purposes of this study, ULN for ALT is 45 IU/L (within 7 days prior to
             enrollment).

          -  Shortening fraction of >= 27% by echocardiogram (within 7 days prior to enrollment).

          -  Ejection fraction of >= 50% by echocardiogram or radionuclide angiogram (within 7 days
             prior to enrollment).

          -  No known contraindication to peripheral blood stem cell (PBSC) collection. Examples of
             contraindications might be a weight or size less than the collecting institution finds
             feasible, 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 >18 months of age with INRG stage L2, MYCN non-amplified, regardless of
             additional biologic features.

          -  Patients with bone marrow failure syndromes.

          -  Patients that are >= 12 and =< 18 months of age with INRG stage M and all 3 favorable
             biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic
             acid [DNA] index > 1) are not eligible.

          -  Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine,
             corticosteroids for reasons other than prevention/treatment of allergic reactions,
             adrenal replacement therapy, etc.) are not eligible.

          -  Female patients who are pregnant are ineligible since fetal toxicities and teratogenic
             effects have been noted for several of the study drugs. A pregnancy test is required
             for female patients of childbearing potential.

          -  Lactating females who plan to breastfeed their infants.

          -  Sexually active patients of reproductive potential who have not agreed to use an
             effective contraceptive method during study therapy and for two months after the last
             dose of ch14.18 (dinutuximab) are not eligible.