Cellular Adoptive Immunotherapy Using Genetically Modified T-Lymphocytes in Treating Patients With Recurrent or Refractory High-Grade Malignant Glioma
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|ClinicalTrials.gov Identifier: NCT00730613|
Recruitment Status : Completed
First Posted : August 8, 2008
Last Update Posted : October 9, 2017
RATIONALE: Cellular adoptive immunotherapy may stimulate the immune system in different ways and stop cancer cells from growing.
PURPOSE: This clinical trial is studying the side effects of cellular adoptive immunotherapy using genetically modified T-lymphocytes and to see how well it works in treating patients with recurrent or refractory high-grade malignant glioma.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors||Biological: therapeutic autologous lymphocytes Genetic: gene expression analysis Other: laboratory biomarker analysis||Phase 1|
- To assess the feasibility and safety of cellular immunotherapy utilizing ex vivo expanded autologous CD8-positive T-cell clones genetically modified to express the IL-13 zetakine chimeric immunoreceptor and the Hy/TK selection/suicide fusion protein in patients with recurrent or refractory, high-grade malignant glioma.
- To evaluate the antitumor activity of adoptively transferred clones in these patients.
- To screen for the development of anti-IL13 zetakine and anti-HyTK immune responses in these patients.
- To evaluate the efficacy of ganciclovir administration for ablating transferred clones in vivo should toxicity be encountered.
- Leukapheresis and therapy preparation: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells. T-cells isolated from the peripheral blood are then genetically modified, hygromycin-resistant cloned, expanded ex vivo, and cryopreserved until the first clinical or radiographic evidence of recurrence or progression. Patients with documented disease recurrence or progression undergo re-biopsy or re-resection of the tumor and placement of a reservoir-access device (Rickham shunt) into the tumor resection cavity prior to autologous T-cell clone infusion therapy.
- Autologous T-cell clone infusion: Patients receive an infusion of autologous antigen-specific CD8+ cytotoxic T-lymphocyte clones over 5-10 minutes on days 1, 3, and 5 of weeks 1 and 2. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving tumor regression with residual disease by MRI after 4 courses of study therapy may receive up to 2 additional courses in the absence of disease progression, unacceptable toxicity, or a complete response.
Patients undergo blood, cerebrospinal fluid, and tissue sample collection periodically for correlative studies. Samples are assessed for IL13Rα2 expression levels, susceptibility to redirected T-cell effector mechanisms, and other tumor and T-cell activation markers.
After completion of study treatment, patients will be followed monthly for 3 months, then every 3 months for two years, and then annually for at least 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones|
|Study Start Date :||February 2002|
|Actual Primary Completion Date :||August 2011|
|Actual Study Completion Date :||August 2011|
Experimental: Treatment (therapeutic autologous lymphocytes)
Patients receive an infusion of autologous antigen-specific CD8+ cytotoxic T-lymphocyte clones over 5-10 minutes on days 1, 3, and 5 of weeks 1 and 2. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
Biological: therapeutic autologous lymphocytes
Cycles of escalating cell dose infusions up to the target cell dose of 10(8)
Genetic: gene expression analysis
At the time of excess pathology samples documenting response/relapse
Other: laboratory biomarker analysis
CSF generated at the time of each T-cell dose
- Feasibility [ Time Frame: 1 year after the end of treatment on study ]
- Safety [ Time Frame: 1 year after the end of treatment on study ]
- Anti-tumor activity of adoptively transferred clones [ Time Frame: 1 year after the end of treatment on study ]
- Anti-IL 13 zetakine and anti-HyTK immune response in patients [ Time Frame: 1 year after the end of treatment on study ]
- Efficacy of ganciclovir for clone ablation (in the event of toxicity) [ Time Frame: 1 year after the end of treatment on study ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00730613
|Principal Investigator:||Stephen Forman, MD||City of Hope Comprehensive Cancer Center|