Inclusion Criteria:

- Patients must have a diagnosis of neuroblastoma either by histologic verification of
neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased
urinary catecholamines

- Patients must have high-risk neuroblastoma

- Disease Status:

- Recurrent/progressive disease at any time - regardless of response to frontline
therapy

- Refractory disease (i.e. less than a partial response to frontline therapy,
including a minimum of 4 cycles of chemotherapy)

- Persistent disease after at least a partial response to frontline therapy: i.e.
patient has had a partial response to frontline therapy but still has residual
disease AND has never had a relapse/disease progression

- Patients must have at least ONE of the following (excluding those patients entered in
the expansion cohort who may be entered on study with no measurable or evaluable
tumor if they have had a prior progression):

- At least one metaiodobenzylguanidine (MIBG) avid bone site or diffuse MIBG
uptake

- Any amount of neuroblastoma tumor cells in the bone marrow based on routine
morphology (with or without immunocytochemistry) in at least one sample from
bilateral aspirates and biopsies; note: patients with < 10% tumor on all samples
from bilateral bone marrow aspirates/biopsies are eligible, but will be
considered separately in definitions of bone marrow response

- At least one measurable soft tissue site on magnetic resonance imaging
(MRI)/computed tomography (CT) scan that is MIBG or positron emission tomography
(PET) avid (if patient known to be MIBG non-avid); measurable is defined as >=
10 mm in at least one dimension

- At least one measurable soft tissue site on MRI/CT scan that is non-avid by MIBG
and PET but that meets either one of the following criteria:

- The lesion has been biopsied at any time point in the past and was
documented to be neuroblastoma AND the lesion has enlarged since the
immediate prior therapy by a minimum of 20% in at least one dimension

- If the lesion is stable or smaller since the last prior therapy then a
biopsy must be performed at least three weeks after the last day of the
last prior therapy that shows neuroblastoma or ganglioneuroblastoma

- Patients must have a life expectancy of at least 6 weeks and a Lansky (=< 16 years)
or Karnofsky (> 16 years) score of at least 50

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to study enrollment

- Patients must not have received the therapies indicated below for the specified time
period prior to the first day of administration of protocol therapy on this study

- Myelosuppressive chemotherapy: must have received last dose at least 2 weeks
prior to protocol therapy; this includes cytotoxic agents given on a low dose
metronomic regimen

- Biologic (anti-neoplastic agent) (includes retinoids): must have received last
dose at least 7 days prior to protocol therapy

- Monoclonal antibodies: must have received last dose at least 7 days or 3
half-lives, whichever is longer, prior to protocol therapy

- Radiation:

- Patients must not have received radiation (small port) for a minimum of two
weeks prior to protocol therapy; tor patients with only one site of measurable
or evaluable disease, radiation must not have been given to that site unless
that site has demonstrated clear progression after radiation, or a biopsy of the
site demonstrated neuroblastoma at least 3 weeks after the last day of radiation

- A minimum of 12 weeks prior to start of protocol therapy is required following
large field radiation therapy (i.e. total body irradiation, craniospinal, whole
abdominal, total lung, > 50% marrow space)

- A minimum of 6 weeks must have elapsed prior to start of protocol therapy for
other substantial bone marrow radiation

- Stem Cell Transplant (SCT):

- Patients are eligible 6 weeks after date of autologous stem cell infusion
following myeloablative therapy (timed from first day of protocol therapy)

- Patients are not eligible post allogeneic stem cell transplant

- Patients who have received an autologous stem cell infusion to support
non-myeloablative therapy (such as 131 iodine [I]-MIBG) are eligible at any time
as long as they meet the other criteria for eligibility

- A minimum of 6 weeks must have elapsed after 131I-MIBG therapy prior to start of
protocol therapy

- Prior anti-GD2 antibody, isotretinoin, or lenalidomide therapy:

- Patients who have received prior anti-GD2 antibody therapy are eligible if they
did not have tumor relapse/progression while receiving this therapy

- Patients who have received either isotretinoin or lenalidomide are eligible, but
not if they have received the two agents concomitantly

- All cytokines or hematopoietic growth factors must be discontinued a minimum of 7
days prior to protocol therapy

- Patients must not be receiving any other anti-cancer agents or radiotherapy at the
time of study entry or while on study

- Absolute phagocyte count (APC = neutrophils and monocytes): >= 1000/mm3

- Absolute neutrophil count: >= 750/mm3

- Platelet count: >= 50,000/mm3, transfusion independent (no platelet transfusions
within 1 week)

- Hemoglobin >= 8.0 (may transfuse)

- Patients with known bone marrow metastatic disease will be eligible for study as long
as they meet hematologic function criteria; patients with marrow disease are not
evaluable for hematologic toxicity

- Age-adjusted serum creatinine =< 1.5 x normal for age AND creatinine clearance or
glomerular filtration rate (GFR) >= 60cc/min/1.73m2

- =< grade 2 hematuria (criteria applicable only for dose levels that include
isotretinoin) and =< grade 2 proteinuria

- Total bilirubin =< 1.5 x upper limit of normal for age

- Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])
< 3 x upper limit of normal (note that for ALT, the upper limit of normal is defined
as 45 U/L)

- Sinusoidal obstruction syndrome (SOS) if present, must be stable or improving
clinically

- Cardiac function:

- Normal ejection fraction (>= 55%) documented by either echocardiogram or
radionuclide multi gated acquisition scan (MUGA) evaluation; OR

- Normal fractional shortening (>= 27%) documented by echocardiogram

- No dyspnea at rest

- Serum triglyceride =< 300mg/dL (applicable only for dose levels that include
isotretinoin) (note that a non-fasting triglyceride value could be obtained, if this
is > 300 mg/dL then a fasting triglyceride should be obtained and patient will be
eligible if the fasting level is < 300 mg/dL)

- =< grade 2 hypercalcemia (applicable only for dose levels that include cis retinoic
acid [RA])

- All post-menarchal females must have a negative beta-human chorionic gonadotropin
(HCG); males and females of reproductive age and childbearing potential must use
effective contraception for the duration of their participation

- Patients with other ongoing serious medical issues must be approved by the study
chair prior to registration

Exclusion Criteria:

- Serum b-HCG must be negative in girls who are post-menarchal; males or females of
reproductive potential may not participate unless they have agreed to use an
effective contraceptive method; pregnant or breast-feeding women will not be entered
on this study

- Breast feeding women are not eligible

- Patients who have an active or uncontrolled infection are excluded

- Patients with a paraben allergy cannot take isotretinoin preparations containing this
compound (ie Accutane, Sotret) but are eligible if they can take an alternate
preparation without paraben; (applicable only for entry onto dose levels receiving
isotretinoin)

- Patients with a history of venous or arterial thrombosis personally or in a first
degree relative before the age of 40 years unless associated with a central line

- Prior allogeneic transplant

- Patients with a history of prior central nervous system (CNS) metastases or skull
lesions with intracranial extension will be required to have a head CT or MRI at
study entry demonstrating no active CNS metastases; patients with skull metastases
with associated intracranial soft tissue masses will remain eligible

- Inability to swallow lenalidomide capsules whole; capsules of 13-isotretinoin may be
opened