Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

June 3, 2015 updated by: City of Hope Medical Center

RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Donor T cells that are treated in the laboratory may be effective treatment for malignant glioma. Aldesleukin may stimulate the white blood cells to kill tumor cells. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best way to give therapeutic donor lymphocytes together with aldesleukin in treating patients with stage III or stage IV malignant glioma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety of GRm13Z40-2 CTL CNS loco-regional cellular immunotherapy in research participants with recurrent or refractory/ progressive malignant glioma (WHO Grades 3 or 4).

II. To assess the safety of convection enhanced delivery (CED) of recombinant human Interleukin-2 (rhuIL-2) used in conjunction with GRm13Z40-2 CTL adoptive transfer.

SECONDARY OBJECTIVES:

I. To investigate the ability of 9-(4-fluoro-3-hydroxy-methyl-butyl) guanine (18FHBG) positron emission tomography PET to image GRm13Z40-2 CTL's in research participants.

II. To study the impact of concurrent dexamethasone administration on the tempo and magnitude of T cell allograft rejection responses in treated research participants by tracking the frequency of anti-GRm13Z40-2 immune responses in serially acquired peripheral blood samples.

III. To evaluate ganciclovir administration for ablating transferred GRm13Z40-2 in vivo should significant graft-mediated toxicities be encountered.

OUTLINE: Patients receive GRm13Z40-2 therapeutic allogeneic lymphocytes intratumorally (IT) over 10 minutes on days 1 and 3 and aldesleukin IT over 3 hours on days 2-5 (days 1-5 in week 2). Treatment repeats every week for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for at least 15 years.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histological verification of grade III or IV MG at original diagnosis
  • Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of radiation therapy
  • Expression of IL13Ralpha2 by immunohistochemistry
  • Karnofsky performance status (KPS) >= 60

  • Disease recurrence/progression in the cerebral hemisphere, which is in at least one area of enhancement amenable to biopsy after protocol enrollment in the following locations:

    • Adjacent or near previous resection cavity
    • Distant from primary location; this includes tumor spread to contralateral hemisphere, corpus callosum, thalamus, basal ganglion, or subependymal locations
  • Research participant has recovered from toxicity of prior therapies; an interval of at least 12 weeks must have elapsed since the completion of radiation therapy; at least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen; and at least 4 weeks since the completion of a non-nitrosourea-containing cytotoxic chemotherapy regimen; if a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose and the start of study treatment, with the exception of bevacizumab where a wash out period of at least 4 weeks is required before starting study treatment
  • History of prior treatment with Temodar if no evidence of intolerance; documentation of intolerance to Temodar is not required
  • Creatinine < 1.6
  • White blood cell (WBC) >= 2,000/dl (or absolute neutrophil count [ANC] > 1,000) Platelets >= 100,000/dl unsupported by transfusion or growth factor, international normalized ratio (INR) < 1.3
  • Bilirubin < 1.5
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) < 2 X upper limits of normal
  • Female research participants of childbearing potential must not be pregnant as evidenced by a serum beta-HCG pregnancy test obtained within 7 days of enrollment
  • Research participants having reproductive potential must agree to use effective contraception during participation on this protocol
  • In the opinion of the neurosurgeon, research participant requires on-going dexamethasone therapy

Exclusion Criteria:

  • Survival expectation less than 4 weeks
  • Pulmonary- Requirement for supplemental oxygen use that is not expected to resolve within 2 weeks, Cardiac- Uncontrolled cardiac arrhythmia, hypotension requiring pressor support, Renal- Dialysis dependent, Neurologic- refractory seizure disorder, clinically evident progressive encephalopathy

  • Tumors with the following characteristics:

    • Large tumor recurrence causing significant symptoms from brain shift or mass effect, and thus not requiring "decompressive" craniotomy
    • Tumors located primarily in the basal ganglion or thalamus
    • Tumors with significant involvement of midbrain, cerebellum, pons and medulla will be excluded due to neurological risks associated with edema exacerbation from therapy
  • Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
  • Positive human immunodeficiency virus (HIV) serology based on testing within 4 weeks of enrollment
  • Research participants being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator
  • Failure to understand the basic elements of the protocol and/or the risks/benefits of participating in this pilot study
  • History of ganciclovir and/or magnetic resonance imaging (MRI) contrast allergy or intolerance History of intolerance to IL-2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
Patients receive intratumoral GRm13Z40-2 therapeutic allogeneic lymphocytes over 10 minutes on days 1 and 3 and intratumoral aldesleukin over 3 hours on days 2-5 (days 1-5 in week 2). Treatment repeats every week for 2 courses in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Optional correlative studies
Procedure: positron emission tomography
Optional correlative studies
Other Names:
  • PET
  • FDG-PET
  • PET scan
  • tomography, emission computed
Biological: therapeutic allogeneic lymphocytes
Given intratumorally
Other Names:
  • ALLOLYMPH
Biological: aldesleukin
Given intratumorally
Other Names:
  • Proleukin
  • IL-2
  • recombinant human interleukin-2
  • recombinant interleukin-2
  • interleukin II
  • TCGF, interleukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety of GRm13Z40-2 CTL CNS loco-regional cellular immunotherapy
Time Frame: Daily for first 2 weeks, weekly for month 1, every other week for month 2 , monthly for 6 months
Daily for first 2 weeks, weekly for month 1, every other week for month 2 , monthly for 6 months
Safety of convection enhanced delivery (CED) of recombinant human Interleukin-2 (rhuIL-2) used in conjunction with GRm13Z40-2 CTL adoptive transfer
Time Frame: Weeks 1 and 2
Weeks 1 and 2
Toxicity as assessed by NCI CTCAE version 4.0
Time Frame: During treatment and up to 21 days after the last GRm13Z40-2 or CED rhuIL-2 infusion
During treatment and up to 21 days after the last GRm13Z40-2 or CED rhuIL-2 infusion

Secondary Outcome Measures

Outcome Measure
Time Frame
Ability of 9-(4-fluoro-3-hydroxy-methyl-butyl) guanine (18FHBG) positron emission tomography PET to image GRm13Z40-2 CTLs
Time Frame: Prior to immunotherapy and 3 weeks post immunotherapy
Prior to immunotherapy and 3 weeks post immunotherapy
Impact of concurrent dexamethasone on the tempo and magnitude of T cell allograft rejection responses by tracking the frequency of anti-GRm13Z40-2 immune responses in serially acquired peripheral blood samples
Time Frame: Post infusion day 1, weeks 2-4 and week 8
Post infusion day 1, weeks 2-4 and week 8
Evaluation of ganciclovir administration for ablating transferred GRm13Z40-2 in vivo should significant graft-mediated toxicities be encountered
Time Frame: When/if grade 3 or 4 toxicity occurs
When/if grade 3 or 4 toxicity occurs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

March 5, 2010

First Submitted That Met QC Criteria

March 8, 2010

First Posted (Estimate)

March 9, 2010

Study Record Updates

Last Update Posted (Estimate)

June 8, 2015

Last Update Submitted That Met QC Criteria

June 3, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07082
  • NCI-2010-00303

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.

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