Cellular Adoptive Immunotherapy Using Genetically Modified T-Lymphocytes in Treating Patients With Recurrent or Refractory High-Grade Malignant Glioma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|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/relapseOther: 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00730613
|Principal Investigator:||Stephen Forman, MD||City of Hope Comprehensive Cancer Center|