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

Trial ID: NCT04214392

Interventional - Phase 1 - Active, not recruiting

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

Interventions

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

Eligibility

Inclusion 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)

Exclusion criteria

• 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)

Sponsor

City of Hope Medical Center, National Cancer Institute (NCI)

Source: ClinicalTrials.gov

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