ACTIVE_NOT_RECRUITING

Chimeric Antigen Receptor (CAR) T Cells With a Chlorotoxin Tumor-Targeting Domain for the Treatment of MMP2+ Recurrent or Progressive Glioblastoma

Conditions

Recurrent Glioblastoma Recurrent Malignant Glioma Recurrent WHO Grade II Glioma Recurrent WHO Grade III Glioma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial studies the side effects and best dose of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain in treating patients with MPP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.

Official Title

A Phase 1 Study to Evaluate Chimeric Antigen Receptor (CAR) T Cells With a Chlorotoxin Tumor-Targeting Domain for Patients With MMP2+ Recurrent or Progressive Glioblastoma

Quick Facts

Study Start:2020-02-26

Study Completion:2025-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04214392

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines. Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with surgery/rickham placement and CAR T cell infusion only after the translated main consent form is signed. * Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval * Karnofsky performance status (KPS) \>= 60% * Eastern Cooperative Oncology Group (ECOG) =\< 2 * Life expectancy \>= 4 weeks * Participant has a prior histologically-confirmed diagnosis of a grade IV glioblastoma, or has a prior histologically-confirmed diagnosis of a grade II or III malignant brain tumors and now has radiographic progression consistent with a grade IV glioblastoma * Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy, and \>= 12 weeks after completion of front-line radiation therapy * City of Hope (COH) Clinical Pathology confirms matrix metalloproteinase (MMP)2+ tumor expression by immunohistochemistry (\>= 20% moderate/high MMP2 \[2+/3+\]) * No known contraindications to leukapheresis, steroids, or tocilizumab * White blood cell (WBC) \> 2000 /dl (or absolute neutrophil count \[ANC\] \>= 1,000/mm\^3) (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Platelets \>= 75,000/mm\^3 (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Hemoglobin \>= 8 g/dl (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Total bilirubin =\< 1.5 upper limit of normal (ULN) (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Aspartate aminotransferase (AST) =\< 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Alanine aminotransferase (ALT) =\< 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Serum creatinine =\< 1.6 mg/dL (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Oxygen (O2) saturation \>= 95% on room air (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo (to be performed within 14 days prior to leukapheresis unless otherwise stated) * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 14 days prior to leukapheresis unless otherwise stated) * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CAR T cells * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)	* Prior and concomitant therapies * Owing to higher frequency of wound-related complications, participants who are within 3 months of having received prior bevacizumab therapy at the time of enrollment are excluded. * Participant has not yet recovered from toxicities of prior therapy * Other illnesses or conditions * Uncontrolled seizure activity and/or clinically evident progressive encephalopathy * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent * Active diarrhea * Clinically significant uncontrolled illness * Active infection requiring antibiotics * Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection * Other active malignancy * Females only: Pregnant or breastfeeding * Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures * Noncompliance * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Inclusion Criteria

Exclusion Criteria

* Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines. Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with surgery/rickham placement and CAR T cell infusion only after the translated main consent form is signed.
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Karnofsky performance status (KPS) \>= 60%
* Eastern Cooperative Oncology Group (ECOG) =\< 2
* Life expectancy \>= 4 weeks
* Participant has a prior histologically-confirmed diagnosis of a grade IV glioblastoma, or has a prior histologically-confirmed diagnosis of a grade II or III malignant brain tumors and now has radiographic progression consistent with a grade IV glioblastoma
* Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy, and \>= 12 weeks after completion of front-line radiation therapy
* City of Hope (COH) Clinical Pathology confirms matrix metalloproteinase (MMP)2+ tumor expression by immunohistochemistry (\>= 20% moderate/high MMP2 \[2+/3+\])
* No known contraindications to leukapheresis, steroids, or tocilizumab
* White blood cell (WBC) \> 2000 /dl (or absolute neutrophil count \[ANC\] \>= 1,000/mm\^3) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Platelets \>= 75,000/mm\^3 (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Hemoglobin \>= 8 g/dl (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Total bilirubin =\< 1.5 upper limit of normal (ULN) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Aspartate aminotransferase (AST) =\< 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Alanine aminotransferase (ALT) =\< 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Serum creatinine =\< 1.6 mg/dL (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Oxygen (O2) saturation \>= 95% on room air (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 14 days prior to leukapheresis unless otherwise stated)
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CAR T cells
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

* Prior and concomitant therapies
* Owing to higher frequency of wound-related complications, participants who are within 3 months of having received prior bevacizumab therapy at the time of enrollment are excluded.
* Participant has not yet recovered from toxicities of prior therapy
* Other illnesses or conditions
* Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
* Active diarrhea
* Clinically significant uncontrolled illness
* Active infection requiring antibiotics
* Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
* Other active malignancy
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
* Noncompliance
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Behnam Badie

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

Behnam Badie, PRINCIPAL_INVESTIGATOR, 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 Registration Dates

Study Start Date2020-02-26

Study Completion Date2025-08-31

Study Record Updates

Study Start Date2020-02-26

Study Completion Date2025-08-31

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Glioblastoma
Recurrent Malignant Glioma
Recurrent WHO Grade II Glioma
Recurrent WHO Grade III Glioma