Biological Therapy and Gene Therapy in Treating Children With Recurrent or Refractory Neuroblastoma
|ClinicalTrials.gov Identifier: NCT00006480|
Recruitment Status : Completed
First Posted : December 31, 2003
Last Update Posted : September 21, 2010
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.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Biological: aldesleukin Biological: therapeutic autologous lymphocytes Drug: chemotherapy Drug: ganciclovir||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Official Title:||Phase I Study to Evaluate the Safety of Cellular Immunotherapy for Recurrent/Refractory Neuroblastoma Using Genetically-Modified Autologous CD8+ T Cell Clones|
|Study Start Date :||May 2000|
|Actual Study Completion Date :||March 2005|
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006480
|United States, California|
|Cancer Center and Beckman Research Institute, City of Hope|
|Duarte, California, United States, 91010-3000|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Study Chair:||Julie R. Park, MD||Fred Hutchinson Cancer Research Center|