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

NCT04214392 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 19309NCI-2019-08393
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Rate and associated 90% Clopper and Pearson binomial confidence limits (90% confidence interval) will be estimated for participants experiencing DLTs at the recommended phase 2 dose schedule. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, and arm. 2. Cytokine Release Syndrome (CRS) 3. All other toxicities.

  28 days

Secondary Outcomes (9)

• Chimeric antigen receptor (CAR) T cell

  15 years

• Endogenous T cell

  15 years

• Cytokine levels in TCF, PB and CSF

  15 years

• Progression free survival time

  At 6 months

• Disease response

  At 6 months

Study Arms (2)

Treatment (CAR T cell therapy) I

EXPERIMENTAL

Arm 1 participants will undergo resection/biopsy of their tumor and placement of a Rickham catheter at the site of the resection/biopsy. Patients receive chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes NCI SYs via single delivery starting on day 0 for 3 weekly cycles over 28 days. Each treatment cycle begins with one CAR T cell infusion delivered intracranial intratumoral or intracavitary \[ICT\] and lasts for 1 week. Beginning 1 week after cycle 3, patients may continue with CAR T cell treatment per principal investigator and patient discretion. Treatment continues in the absence of disease progression or unacceptable toxicity.

Biological: Chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes (via ICT delivery)

Treatment (CAR T cell therapy) II

EXPERIMENTAL

Arm 2 participants will undergo resection/biopsy of their tumor and placement of a Rickham catheter at the site of the resection/biopsy and the lateral ventricle. Patients receive chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes NCI SYs via dual delivery starting on day 0 for 3 weekly cycles over 28 days. Each treatment cycle begins with two CAR T cell infusions (intracranial intratumoral or intracavitary \[ICT\]) and also into the lateral ventricle (intracranial intraventricular \[ICV\]) and lasts for 1 week. Beginning 1 week after cycle 3, patients may continue with CAR T treatment per principal investigator and patient discretion. Treatment continues in the absence of disease progression or unacceptable toxicity.

Biological: Chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes (via ICT/ICV dual delivery)

Interventions

Chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes (via ICT delivery) BIOLOGICAL

Given via ICT delivery

Also known as: Chlorotoxin-CD28-CD3z-CD19t-expressing CAR T-cells

Treatment (CAR T cell therapy) I

Chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes (via ICT/ICV dual delivery) BIOLOGICAL

Given via ICT/ICV dual delivery

Also known as: Chlorotoxin-CD28-CD3z-CD19t-expressing CAR T-cells

Treatment (CAR T cell therapy) II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Chlorotoxin

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Behnam Badie

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2019
• First Posted: January 2, 2020
• Study Start: February 26, 2020
• Primary Completion (Estimated): June 9, 2026
• Study Completion (Estimated): June 9, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-10

Locations

US (1)