RATIONALE: Inserting the gene for interleukin-2 into a person's neuroblastoma cells may make the body build an immune response and kill tumor cells. PURPOSE: Phase I trial to study the effectiveness of using interleukin-2 gene-modified neuroblastoma cells in treating children who have refractory or recurrent neuroblastoma.

Condition	Treatment or Intervention	Phase
recurrent neuroblastoma	Procedure: biological response modifier therapy  Vaccine: tumor cell derivative vaccine  Procedure: gene therapy  Procedure: vaccine therapy	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety in children of recurrent neuroblastoma of two weekly subcutaneous injections of autologous, or partially HLA-matched allogeneic, neuroblastoma cells that have been modified by insertion of the interleukin-2 gene introduced by a retroviral vector. II. Determine whether multiple histocompatibility-restricted or unrestricted antitumor immune responses are induced by this treatment and the cell dose required to produce these effects. III. Obtain preliminary data on the antitumor effects of this regimen.

PROTOCOL OUTLINE: Autologous or partially HLA-matched allogeneic neuroblastoma cells are transduced with a human gene for interleukin-2 production. Patients receive subcutaneous injections of the gene-modified cells on days 1 and 8, with the second injection containing 10 times more cells than the first injection. After a 3-4 week rest, stable and responding patients may receive additional weekly injections at the second dose. Cohorts of 3-6 patients will be entered at increasing cell doses until the maximum tolerated dose is estimated. Multiple injection sites may be used at the higher cell-dose levels. Patients are followed every week for 6 weeks, every other week for 6 weeks, and monthly for 1 year. Additional visits may be required as clinically indicated.

PROJECTED ACCRUAL: Approximately 12 patients each will be entered into the autologous and the partially HLA-matched allogeneic tumor cell treatment groups. Accrual is expected to require 4 years for the autologous tumor cell group and 2 years for the partially HLA-matched allogenic tumor cell group.

Ages Eligible for Study:  up to  21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven high risk neuroblastoma at the completion of planned primary therapy; No rapidly progressing disease
• Allogeneic transduced cell line available; Demonstrated production of at least 150 picograms of interleukin-2 per 10 to the 6th cells per day

--Prior/Concurrent Therapy--

• See Disease Characteristics; Recovered from prior chemotherapy; No concurrent antibiotics except prophylactic trimethoprim/sulfamethoxazole; No concurrent drugs other than analgesics

--Patient Characteristics--

• Age: Under 21 at diagnosis
• Performance status: ECOG 0-2
• Life expectancy: At least 8 weeks
• Hematopoietic: (unless marrow replaced by tumor); Absolute neutrophil count greater than 500/mm3; Platelet count greater than 50,000/mm3
• Hepatic: Bilirubin less than 1.5 mg/dL; AST no greater than 2 times normal; PT normal
• Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than 80 mL/min; Urinalysis normal
• Metabolic: Electrolytes (including calcium, phosphate) normal; Glucose normal; Weight greater than 10th percentile for age; Albumin greater than 3 g/dL
• Other: No active infection; HIV negative; Not pregnant or nursing

Tennessee
      Saint Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States

Study chairs or principal investigators

Gregory Hale,  Study Chair,  St. Jude Children's Research Hospital   

Study ID Numbers:  CDR0000064681; SJCRH-CYGENE; NCI-H96-0005; SJCRH-CYGNE2
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002748
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08