Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma
Condition: Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Recurrent Neuroblastoma; Regional Neuroblastoma; Stage 4 Neuroblastoma; Stage 4S Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: Aldesleukin; Dinutuximab; Isotretinoin; Laboratory Biomarker Analysis; Pharmacological Study; Quality-of-Life Assessment; Sargramostim
Intervention description: Given IV; Given IV; Given PO; Correlative studies; Correlative studies; Ancillary studies; Given IV or SC
Intervention MeSH terms: Vitamin A; Aldesleukin; Interleukin-2; Tretinoin; Dinutuximab; Isotretinoin; Sargramostim; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1449.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No

Summary:

      This partially randomized phase III trial studies isotretinoin with dinutuximab, aldesleukin,
      and sargramostim to see how well it works compared to isotretinoin alone following stem cell
      transplant in treating patients with neuroblastoma. Drugs used in chemotherapy, such as
      isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal
      antibodies, such as dinutuximab, may block tumor growth in different ways by targeting
      certain cells. Aldesleukin and sargramostim may stimulate a person's white blood cells to
      kill cancer cells. It is not yet known if chemotherapy is more effective with or without
      dinutuximab, aldesleukin, and sargramostim following stem cell transplant in treating
      neuroblastoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must be diagnosed with neuroblastoma, and categorized as high risk at the
             time of diagnosis; exception: patients who are initially diagnosed as non-high-risk
             neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are
             also eligible

          -  All patients must have completed therapy including intensive induction followed by
             ASCT and radiotherapy to be eligible for ANBL0032; radiotherapy may be waived for
             patients who either have small adrenal masses which are completely resected up front,
             or who never have an identifiable primary tumor; examples of such therapies include:

               -  Following treatment per A3973 protocol

               -  Following treatment per Pediatric Oncology Group (POG)-9341/9342 protocol

               -  Following treatment per CCG3891

               -  Following treatment on New Approaches to Neuroblastoma Therapy (NANT) 2001-02

               -  Enrollment on or following treatment per ANBL02P1

               -  Enrollment on or following treatment per ANBL07P1

               -  Tandem transplant patients are eligible:

                    -  Following treatment on or per ANBL0532

                    -  Following treatment per POG 9640

                    -  Following treatment per COG ANBL00P1

                    -  Following treatment per CHP 594/Dana-Farber Cancer Institute (DFCI) 34-DAT

          -  No more than 12 months from the date of starting the first induction chemotherapy
             after diagnosis to the date of ASCT except for the rare occasions as noted below; for
             tandem ASCT patients, this will be the date of the FIRST stem cell infusion;
             exception: for those who are initially diagnosed as non-high risk neuroblastoma, but
             later converted (and/or relapsed) to high risk neuroblastoma, the 12 months
             restriction should start from the date of induction therapy for high risk
             neuroblastoma (not from the initial induction therapy for non-high risk disease), to
             the date of ASCT

          -  At pre-ASCT evaluation patients must meet the International Neuroblastoma Response
             Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases and bone
             metastases; patients who meet those criteria must also meet the protocol specified
             criteria for bone marrow response as outlined below:

               -  =< 10% tumor (of total nucleated cellular content) seen on any specimen from a
                  bilateral bone marrow aspirate/biopsy

               -  Patient who have no tumor seen on the prior bone marrow, and then have =< 10%
                  tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT
                  and/or pre-enrollment evaluation will also be eligible (note that per INRC this
                  would have been defined as "overall" response of progressive disease [PD])

          -  Prior to enrollment on ANBL0032, a determination of mandatory disease staging must be
             performed (tumor imaging studies including computed tomography [CT] or magnetic
             resonance imaging [MRI], MIBG scan, and vanillylmandelic acid [VMA]/homovanillic acid
             [HVA]; bone marrow aspirates are required but biopsy may be omitted if negative prior
             to ASCT); this disease assessment is required for eligibility and should be done
             preferably within 2 weeks, but must be done within a maximum of 4 weeks before
             enrollment

               -  For those with residual disease before radiotherapy, re-evaluation of irradiated
                  residual tumors is preferably performed at the earliest 5 days after completing
                  radiotherapy; patients with residual disease are eligible; biopsy is not
                  required; patients who have biopsy proven residual disease after ASCT will be
                  enrolled on Stratum 07

               -  Patients must not have progressive disease at the time of study enrollment except
                  for protocol specified bone marrow response and except for elevations of
                  catecholamines as the only sign of disease in a patient who had normal
                  catecholamines at pre-ASCT evaluation

          -  Patients must be enrolled before treatment begins; the date protocol therapy is
             projected to start must be no later than ten (10) calendar days after the date of
             study enrollment; patients should be enrolled preferably between day 56 and day 85
             after peripheral blood stem cell (PBSC) infusion (day from 2nd stem cell infusion for
             tandem transplant); patients must be enrolled no later than day 200 after PBSC
             infusion; enrollment must occur after completion of radiotherapy, and after completion
             of tumor assessment post-ASCT and radiotherapy; informed consent should be obtained
             within 3 weeks pre-ASCT up to the time of registration

          -  Patients must not have received prior anti-disialoganglioside (GD2) antibody therapy

          -  Patients must have a Lansky or Karnofsky performance scale score of >= 50% and
             patients must have a life expectancy of >= 2 months

          -  Total absolute phagocyte count (APC = %neutrophils + %monocytes) X white blood cell
             (WBC) is at least 1000/uL

          -  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:

               -  No greater than 0.4 mg/dL (1 month to < 6 months)

               -  No greater than 0.5 mg/dL (6 months to < 1 year)

               -  No greater than 0.6 mg/dL (1 to < 2 years)

               -  No greater than 0.8 mg/dL (2 to < 6 years)

               -  No greater than 1.0 mg/dL (6 to < 10 years)

               -  No greater than 1.2 mg/dL (10 to < 13 years)

               -  No greater than 1.4 mg/dL (>= 13 years [female])

               -  No greater than 1.5 mg/dL (13 to < 16 years [male])

               -  No greater than 1.7 mg/dL (>= 16 years [male])

          -  Total bilirubin =< 1.5 x normal

          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x
             normal

          -  Veno-occlusive disease, if present, should be stable or improving

          -  Shortening fraction of >= 27% by echocardiogram, or if shortening fraction abnormal,
             ejection fraction of >= 55% by gated radionuclide study or echocardiogram; note: the
             echocardiogram or gated radionuclide study must be performed within 4 weeks prior to
             enrollment

          -  Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) > 60%
             predicted by pulmonary function test; for children who are unable to do pulmonary
             function tests (PFTs), no evidence of dyspnea at rest and no exercise intolerance
             should be documented; note: the pulmonary function test must be performed within 4
             weeks prior to enrollment

          -  Patients with seizure disorder may be enrolled if on anticonvulsants and
             well-controlled; central nervous system (CNS) toxicity < grade 2

          -  Written informed consent in accordance with institutional and Food and Drug
             Administration (FDA) guidelines must be obtained from parent or legal guardian

          -  Females of childbearing potential must have a negative pregnancy test; patients of
             childbearing potential must agree to use an effective birth control method; female
             patients who are lactating must agree to stop breast-feeding