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

Primary Purpose

Brain and Central Nervous System Tumors

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

therapeutic autologous lymphocytes

gene expression analysis

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult anaplastic astrocytoma, adult diffuse astrocytoma, adult pilocytic astrocytoma, adult subependymal giant cell astrocytoma, adult anaplastic ependymoma, adult ependymoma, adult myxopapillary ependymoma, adult subependymoma, adult anaplastic oligodendroglioma, adult oligodendroglioma, adult brain stem glioma, adult giant cell glioblastoma, adult glioblastoma, recurrent adult brain tumor, adult gliosarcoma, adult mixed glioma, adult pineal gland astrocytoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (therapeutic autologous lymphocytes)

Arm Description

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.

Outcomes

Primary Outcome Measures

Feasibility

Safety

Secondary Outcome Measures

Anti-tumor activity of adoptively transferred clones

Anti-IL 13 zetakine and anti-HyTK immune response in patients

Efficacy of ganciclovir for clone ablation (in the event of toxicity)

Full Information

NCT ID

NCT00730613

First Posted

August 7, 2008

Last Updated

October 6, 2017

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00730613

Brief Title

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

Official Title

Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

February 2002 (undefined)

Primary Completion Date

August 2011 (Actual)

Study Completion Date

August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain and Central Nervous System Tumors

Keywords

adult anaplastic astrocytoma, adult diffuse astrocytoma, adult pilocytic astrocytoma, adult subependymal giant cell astrocytoma, adult anaplastic ependymoma, adult ependymoma, adult myxopapillary ependymoma, adult subependymoma, adult anaplastic oligodendroglioma, adult oligodendroglioma, adult brain stem glioma, adult giant cell glioblastoma, adult glioblastoma, recurrent adult brain tumor, adult gliosarcoma, adult mixed glioma, adult pineal gland astrocytoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (therapeutic autologous lymphocytes)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

therapeutic autologous lymphocytes

Intervention Description

Cycles of escalating cell dose infusions up to the target cell dose of 10(8)

Intervention Type

Genetic

Intervention Name(s)

gene expression analysis

Intervention Description

At the time of excess pathology samples documenting response/relapse

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

CSF generated at the time of each T-cell dose

Primary Outcome Measure Information:

Title

Feasibility

Time Frame