Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma

Not Recruiting

Trial ID: NCT00026312,29,26500,45600


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.

Official Title

Phase III Randomized Study of Chimeric Antibody 14.18 (Ch14.18) in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue

Stanford Investigator(s)


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

      - 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

   - 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

   - 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


biological: sargramostim

biological: aldesleukin

other: laboratory biomarker analysis

other: pharmacological study

drug: isotretinoin

other: quality-of-life assessment

biological: Dinutuximab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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