PRIMARY OBJECTIVE To determine the percentage of patients with high risk neuroblastoma in first or subsequent partial response or better, or with microscopic residual bone marrow disease, who demonstrate an immunological anti-tumor response at any time during, and for up to 12 months from initiation of, treatment with subcutaneous injections of autologous neuroblastoma cells, genetically modified by adenoviral vectors to secrete interleukin-2 (IL-2) (autologous neuroblastoma vaccine)

SECONDARY OBJECTIVES 1. To determine the toxicity of the autologous neuroblastoma vaccine given according to this schedule 2. To obtain preliminary data on the effect of vaccine administration on progression-free survival from high-risk neuroblastoma

Condition	Treatment or Intervention	Phase
Neuroblastoma	Vaccine: autologous neuroblastoma vaccine  Drug: IL-2	Phase I Phase II

Further Study Details: 

Expected Total Enrollment:  15

Tumor cells from subjects with high-risk neuroblastoma will be obtained at the time of presentation and initial diagnosis, during routine surveillance of bone marrow disease status, or at the time of surgical resection of disease during primary chemotherapy. The tumor cells will be irradiated to prevent the possibility of tumor growth. Autologous neuroblastoma tumor cells will be used to treat neuroblastoma following the completion of primary or salvage chemotherapy when peripheral blood lymphocyte counts have recovered to > 500 CD3+ cells/mm3. This preceding chemotherapy may or may not have included bone marrow or peripheral stem cell rescue. Therefore, following the achievement of best response with chemotherapy, vaccine will be administered for 6 months. Vaccine modified for secretion of IL-2 will be used.

Vaccine therapy will commence after complete recovery from the side effects of primary or salvage chemotherapy, as long as the subject has an absolute CD3+ lymphocyte count and an absolute neutrophil count greater than 500/mm3. A vaccine consisting of 0.3 x 10 8 cells/patient will be given per injection, based on data from the Phase I studies. Injections will be given twice monthly for two months, then monthly for four months, for a total of eight vaccine injections over six months. The immune effects of the vaccine, toxicity of treatment, and anti-tumor effects will be periodically assessed. Further evaluation will be done annually.

The first and second vaccine injection sites will be “punch biopsied” one week after the injection. Several x-rays and various types of scans will also be taken to assist with monitoring the status of the neuroblastoma. Complete details of the evaluations required by this study are included in.

Subjects may receive supportive care for any acute or chronic toxicity from the injections, including blood product support, antibiotics, and other appropriate intervention. Pneumocystis carinii prophylaxis initiated during chemotherapy may be continued during vaccine therapy for as long as deemed appropriate by the investigator. As well, subjects may receive concurrent therapy with cis-retinoic acid at the discretion of the treating physician.

An adenoviral vector is being used to transduce the cells ex-vivo. Subjects will not be treated with the viral vector.

Ages Eligible for Study:  up to  64 Years,  Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:

• Patients with high risk neuroblastoma defined below, who, following completion of front-line or salvage chemotherapy that may or may not have included high-dose chemotherapy followed by peripheral blood stem cell or bone marrow rescue with or without cis-retinoic acid, have achieved partial response or better, or who have microscopic residual bone marrow:

a) INSS Stage 4 neuroblastoma, diagnosed between 1 and 21 years of age (inclusive)

b) INSS Stage 3, N-myc amplified neuroblastoma, diagnosed between 1 and 21 years of age (inclusive)

c) INSS Stage 3, N-myc non-amplified, Shimada unfavorable histology neuroblastoma, diagnosed between 1 and 21 years of age (inclusive)

d) INSS Stages 2A or 2B, N-myc amplified, Shimada unfavorable histology, diagnosed between 1 and 21 years of age (inclusive)

e) INSS Stage 4 neuroblastoma, with Shimada unfavorable histology, diagnosed under 365 days of age

• Patients with intermediate or low risk neuroblastoma, who have achieved a second or subsequent partial response or better following chemotherapy treatment of first or subsequent relapse
• Patients must have recovered from the toxic effects of prior chemotherapy prior to treatment on this study, and must have both an absolute lymphocyte count and an absolute neutrophil count greater than 500/mm3.
• Patients with disease status outlined in the first bullet who have been treated with allogeneic tumor vaccine are eligible for treatment with autologous tumor vaccine when that product becomes available
• Patients may not concurrently receive any investigational agents or other tumor vaccines.
• Patients must be HIV-negative.
• Female patients must not be pregnant or lactating.
• Patients must have autologous transduced neuroblastoma cells available that are demonstrably producing > 150 pg IL-2/10e6 cells/24 hours.
• Patients or legal guardians must sign an informed consent according to institutional guidelines.
• Patients who are sexually active must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom.

Texas
      Texas Children's Hospital, Houston,  Texas,  77030,  United States

Study chairs or principal investigators

Heidi V Russell, MD,  Principal Investigator,  Baylor College of Medicine   

Study ID Numbers:  H8354; HIGH RISK NEUROBLASTOMA
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  October 30, 2002
ClinicalTrials.gov Identifier:  NCT00048386
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08