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Cellular Adoptive Immunotherapy Using Genetically Modified T-Lymphocytes in Treating Patients With Recurrent or Refractory High-Grade Malignant Glioma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 70 Years
Gender All
More Inclusion & Exclusion Criteria

DISEASE CHARACTERISTICS:

  • - Histologically confirmed malignant glioma at original diagnosis.
  • - Grade III or IV disease.
  • - Refractory or recurrent disease.
  • - Unifocal site of original disease in cerebral cortex.
  • - No clinical evidence of progressive encephalopathy.
  • - Has not undergone recent re-resection of recurrent or progressive disease.
  • - No communication between the tumor resection cavity and the ventricles and deep cerebrospinal fluid pathways as documented by post-operative MRI scan.
PATIENT CHARACTERISTICS:
  • - Karnofsky performance status 70-100% - Life expectancy > 3 months.
  • - WBC ≥ 2,000/dL.
  • - ANC > 1,000/dL.
  • - Platelet count ≥ 100,000/dL (unsupported by transfusion or growth factor) - Creatinine < 1.6 mg/dL.
  • - Bilirubin < 1.5.
  • - SGOT and SGPT < 2 times upper limit of normal.
  • - Not pregnant.
  • - Negative pregnancy test.
  • - Fertile patients must use effective contraception.
  • - Able to understand protocol basic elements and/or risks/benefits of participating in this pilot study.
  • - No requirement for supplemental oxygen to keep saturation > 95% that is not expected to resolve within 2 weeks.
  • - No uncontrolled cardiac arrhythmia.
  • - No hypotension requiring pressor support.
  • - No renal dialysis dependency.
  • - No refractory seizure disorder.
  • - No concurrent non-malignant illness that is poorly controlled with treatment or is of such severity the investigators deem it unwise to enter the patient on protocol.
  • - No severe infection for which patient is being treated.
  • - No history of ganciclovir and/or Prohance contrast allergy or intolerance.
  • - No HIV positivity within the past 3 months.
PRIOR CONCURRENT THERAPY:
  • - See Disease Characteristics.
  • - Must have recovered from major surgery.
  • - At least 4 weeks since primary therapy and no steroid dependence.
  • - At least 2 weeks since prior adjuvant cytotoxic chemotherapy and recovered.
  • - No concurrent systemic corticosteroids, except for use in managing T-cell therapy toxicity.
  • - No concurrent immunotherapy (i.e., interferons, vaccines, or other cellular products) - No concurrent pentoxifylline.
  • - No other concurrent investigative agents.
  • - No concurrent ganciclovir or ganciclovir derivative.
- No concurrent acyclovir for non-life threatening herpes virus infection

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00730613
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

City of Hope Medical Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Stephen Forman, MD
Principal Investigator Affiliation City of Hope Comprehensive Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Completed
Countries
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain and Central Nervous System Tumors
Additional Details

OBJECTIVES: Primary.

  • - 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.
Secondary.
  • - 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.
OUTLINE:
  • - 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.

Arms & Interventions

Arms

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.

Interventions

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

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

For additional contact information, you can also visit the trial on clinicaltrials.gov.