Clinical Trial Finder

INCLUSION CRITERIA:

• - Histologically proven high risk neuroblastoma in first or subsequent relapse or with primary refractory disease or inability to complete standard therapy.

• - Age less than 21 at time of initial diagnosis.

• - Life expectancy 12 weeks or greater.

• - Karnofsky or Lansky score of 50 or greater.

• - Platelet count of 50,000/ul or greater.

• - ANC greater than 750/ul.

• - Alk Phos level less than 2.5 x upper limit of normal.

• - Bilirubin less than 2x normal.

• - AST less than 3x normal.

• - Hgb 8.0 or greater.

• - Creatinine 2 x ULN or less OR GFR greater than 40 ml/min/1.73 m2.

• - Patient has recovered from last chemotherapy or investigational therapy prior to study enrollment.

• - Women of child-bearing potential must not be pregnant and take/use effective birth control while participating in the study.

EXCLUSION CRITERIA:

• - Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded from this research.

• - Women who are breast-feeding.

• - Known HIV positive subjects since treatment may be immunosuppressive.

• - Severe intercurrent infection or uncontrolled condition including, but not limited to ongoing or active infection, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• - Previous use of oral cytoxan for more than 2 consecutive months within the last 6 months.

• - Patients currently receiving any investigational agents or have received any tumor vaccines within the previous six months.

- Patients, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

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.

Arms

Experimental: Treatment Plan

Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells) and Cytoxan (Cyclophosphamide)

Interventions

Biological: - Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells

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.