Biological Therapy and Gene Therapy in Treating Children With Recurrent or Refractory Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Biological therapies use different ways to stimulate the immune system and stop
      cancer cell from growing. Inserting genetic material made in the laboratory into a person's
      blood cells may make the body build an immune response to kill tumor cells.

      PURPOSE: Phase I trial to study the effectiveness of biological therapy and gene therapy in
      treating children who have recurrent or refractory neuroblastoma.
    

Detailed description: 
      OBJECTIVES: I. Determine the safety and toxicity of cellular immunotherapy using ex vivo
      expanded autologous CD8+ cytotoxic T-lymphocyte clones genetically modified to express the
      CE7R scFvFc:zeta chimeric immunoreceptor and the HyTK selection/suicide gene in children with
      recurrent or refractory disseminated neuroblastoma. II. Determine the antitumor activity of
      this regimen in these patients. III. Determine the duration of in vivo persistence of
      adoptively transferred clones and the effect of interleukin-2 on maintaining the in vivo
      persistence of these clones. IV. Screen for the development of host anti-scFvFc:zeta and HyTK
      immune responses in patients treated with this regimen. V. Determine the efficacy of
      ganciclovir in ablating transferred clones in vivo if toxicity occurs in these patients.

      OUTLINE: This is a multicenter study. Patients undergo autologous peripheral blood stem cell
      harvest. CD8+ cytotoxic T-lymphocyte (CTL) clones are isolated, genetically modified to
      express the CE7R scFvFc:zeta chimeric immunoreceptor and the HyTK selection/suicide gene, and
      then expanded ex vivo. While the modified CTL clones are being generated, patients each
      receive an individualized salvage chemotherapy regimen that may consist of one of the
      following: cyclophosphamide and topotecan; ifosfamide, carboplatin, and etoposide; or another
      chemotherapy regimen chosen by the patient's primary oncologist. The first cohort of 5
      patients receives escalating doses of modified CTL clones IV over 30 minutes on days 0, 14,
      and 28 in the absence of disease progression or unacceptable toxicity. Each patient begins
      the series of 3 infusions as soon as an adequate number of modified CTL clones are ready and
      after the acute side effects of chemotherapy have resolved. In the absence of unacceptable
      toxicity in the first cohort, the second cohort of 5 patients receives the same treatment as
      cohort 1 plus interleukin-2 subcutaneously every 12 hours on days 15-24 and 29-38. Patients
      with unacceptable toxicity receive ganciclovir IV every 12 hours for 14 days (or longer if
      symptomatic resolution is not achieved in that interval). Patients are followed at day 100
      and then periodically thereafter.

      PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 3 years.
    

Intervention name(s): aldesleukin; therapeutic autologous lymphocytes; chemotherapy; ganciclovir
Intervention type(s): Biological; Biological; Drug; Drug
Intervention MeSH terms: Aldesleukin; Ganciclovir; Ganciclovir triphosphate
Primary purpose: Treatment
Keywords: disseminated neuroblastoma; recurrent neuroblastoma