• Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  Phase I Primary Objective: Evaluate the safety of fixed dose oral cytoxan administered metronomically to coincide with repeated immunizations of gene-modified, IL-2/lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-LTN cells co-administered with unmodified SKNLP neuroblastoma cell lines in patients with a history of relapsed/refractory high-risk neuroblastoma.
  
  
• Number of Participants with Disease Progression as a Measure of Efficacy [ Time Frame: 15 years ] [ Designated as safety issue: No ]
  Phase II Primary Objective: Evaluate time to progression after administration of combination metronomic chemotherapy and allogeneic tumor cell immunizations in patients with a history of relapsed/refractory high-risk neuroblastoma.
  
  

• Participants with T-cell changes as a Measure of Immune Response [ Time Frame: 15 years ] [ Designated as safety issue: No ]
  Phase I Secondary Objective: Evaluate the immune response to combination metronomic chemotherapy and allogeneic tumor cell immunizations.
  
  
• Analysis of Immunologic Measurements [ Time Frame: 15 years ] [ Designated as safety issue: No ]

  Phase II Secondary Objectives:

  1. Evaluate changes in T regulatory cell absolute number, percentages, and suppressive function after the use of metronomic low-dose oral cytoxan with allogeneic neuroblastoma tumor cell immunizations.
  2. Evaluate the alterations in angiogenic biomarkers related to fixed dose oral cytoxan and repeated immunizations with allogeneic tumor cell immunizations.
  
  

Biological: Neuroblastoma Vaccine

1x10^7cells/m2 each of unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells will be given by subcutaneous injection while suspended in Ringers solution with 5% HSA in a single syringe in a volume of up to 1 ml.

Vaccines will be given on day 0 of week 0 and then on day 0 (+ 72 hours) of weeks 2, 4, 6, 9, 12, 16, 20.

Cells will be administered as a subcutaneous injection over 1 minute using a 21-gauge needle. Procedural pain control methods may be used per institutional protocol.

Drug: Cytoxan
Metronomic oral cytoxan will start 72 hours prior to the first vaccination at a dose of 50 mg/m2/day. Cytoxan will be held on the day of vaccine administration and for the next 96 hours. After the first vaccine, patients will take 25 mg/m2/day as outlined on the roadmap.

WHAT IS THE OVERALL TREATMENT PLAN AND HOW MANY VACCINATIONS WILL THE PATIENT RECEIVE? There will be several injections of the vaccine scheduled. The first injection will be given 3 days after starting oral cytoxan. The 2nd to 4th injections will be given approximately every 14 days after the previous vaccine. During this time, the patient will be taking oral cytoxan once a day except on the day of and 4 days following the vaccine. Two to 3 weeks after the 4th vaccine, the patient will have a complete evaluation of their disease. If the scans and lab tests show that the patient has not had any serious side-effects, they will be eligible to receive 4 additional vaccinations given at 3 week intervals. The disease will be re-evaluated again after vaccine numbers 6 and 8. If the patient is able to complete the entire study, they will have received a total of 8 vaccinations and the last dose of oral cytoxan will be 1 month after the 8th vaccination. Total time duration for participating in this study is 15 years (treatment portion within year 1 and follow up during years 2-15).

Neuroblastoma vaccinations are given like many other vaccines. They will be given subcutaneously. The injections will be 1/10th of a teaspoon.

MEDICAL TESTS BEFORE STARTING TREATMENT:

Before starting low dose chemotherapy plus oral cytoxan, patients will receive a series of standard medical tests:

• Physical exam
• Blood tests to measure blood cells, blood salts, kidney and liver function
• Measurements of their disease (CT or MRI of the primary tumor site and any locations of tumor spread; MIBG or Bone scan; Chest X-ray if they did not have a CT of the chest; and bone marrow studies if the patient has known bone marrow disease)
• Baseline testing of immune function
• Pregnancy testing will be performed on females of child bearing age

MEDICAL TESTS DURING AND AFTER TREATMENT:

Prior to each vaccine dose, the patient will receive:

• Physical exam
• Blood tests to measure blood cells, blood salts, kidney and liver function
• Measurements of the disease (CT or MRI of the primary tumor site and any locations of tumor spread; MIBG or Bone scan; Chest X-ray if they did not have a CT of the chest; and bone marrow studies if they have known bone marrow disease) after the 4th, 6th and 8th vaccine.
• Testing of immune function
• Pregnancy testing will be performed again on females of child bearing age prior to the 5th vaccine

To learn more about the way the vaccine is stimulating the immune cells, we will collect blood prior to each vaccination and at scheduled time points until 3 months after the last vaccine treatment. The total amount of blood to be collected on any day is no more than 2 ounces, but will depend upon the weight. This volume is considered safe in teens and adults, but may be decreased if the patient is anemic. On days when the patient receives the vaccine, blood will be taken before the cells are given.