- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00006480
Biological Therapy and Gene Therapy in Treating Children With Recurrent or Refractory Neuroblastoma
Phase I Study to Evaluate the Safety of Cellular Immunotherapy for Recurrent/Refractory Neuroblastoma Using Genetically-Modified Autologous CD8+ T Cell Clones
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Duarte, California, United States, 91010-3000
- Cancer Center and Beckman Research Institute, City of Hope
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Washington
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Seattle, Washington, United States, 98109-1024
- Fred Hutchinson Cancer Research Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS: Histologically and/or radiographically proven disseminated neuroblastoma Recurrent or refractory to first-line therapy as defined by less than complete response to standard induction chemotherapy combined with surgical resection Histologic verification of neuroblastoma required at original diagnosis No radiographically detectable CNS involvement No clinically evident progressive encephalopathy
PATIENT CHARACTERISTICS: Age: 1 to 17 (children only) Performance status: Not specified Life expectancy: At least 3 months Hematopoietic: Not specified Hepatic: Not specified Renal: No dialysis dependency Cardiovascular: No uncontrolled cardiac arrhythmia No hypertension requiring pressor support Pulmonary: No requirement for supplemental oxygen unless expected to resolve within 2 weeks Neurologic: See Disease Characteristics No refractory seizure disorder Other: No detectable human antimouse antibody reactivity if received prior murine antibody preparations No history of ganciclovir allergy or intolerance HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 2 months after study
PRIOR CONCURRENT THERAPY: Biologic therapy: No other concurrent antibody therapy during or after study No other concurrent immunotherapy (e.g., interferons, vaccines, or other cellular products) Chemotherapy: At least 3 weeks since prior standard or experimental chemotherapy and recovered Endocrine therapy: No concurrent systemic corticosteroids unless specifically for amelioration of toxicity induced by transferred T-cell therapy Radiotherapy: Not specified Surgery: Not specified Other: At least 3 weeks since prior immunosuppressive therapies and recovered No concurrent pentoxifylline No other concurrent investigational agents No concurrent ganciclovir, any ganciclovir derivatives, or acyclovir for non-life-threatening herpes virus infections
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Julie R. Park, MD, Fred Hutchinson Cancer Center
Study record dates
Study Major Dates
Study Start
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Neuroblastoma
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Antineoplastic Agents
- Aldesleukin
- Ganciclovir
- Ganciclovir triphosphate
Other Study ID Numbers
- 1524.00
- FHCRC-1524.00
- NCI-H00-0065
- CDR0000068310 (REGISTRY: PDQ)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neuroblastoma
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingStage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 Neuroblastoma | Stage 1 Neuroblastoma | Stage 2 NeuroblastomaUnited States, Canada, Australia, New Zealand
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Stage 4S Neuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand
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National Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)RecruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States, Puerto Rico, Canada, Australia, New Zealand, Netherlands, Saudi Arabia, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4 NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Stage 4S NeuroblastomaUnited States
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