CAR T Cells in Patients With MMP2+ Recurrent or Progressive Glioblastoma

Trial Title: CAR T Cells in Patients With MMP2+ Recurrent or Progressive Glioblastoma

NCT ID: NCT05627323

Condition: Glioblastoma Multiforme of Brain

Conditions: Official terms:
Glioblastoma

Conditions: Keywords:
Progressive or recurrent glioblastoma
MMP2+

Study type: Interventional

Study phase: Phase 1

Overall status: Active, not recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Intervention model description: Two dose levels investigated, with both dose levels proceeding in parallel. Expansion or de-escalation decision rules are based on a traditional 3+3 clinical study design.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: CHM-1101 CAR-T cells
Description: Administered via ICT/ICV dual delivery
Arm group label: Treatment (CAR T cell therapy) 1
Arm group label: Treatment (CAR T cell therapy) 2

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

Other name: Chlorotoxin-CD28-CD3z-CD19t-expressing CAR T-cells

Summary: This is a phase 1b study to evaluate the safety of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain (ie, CHM-1101, the study treatment) to determine the best dose of CHM-1101, and to assess the effectiveness of CHM-1101 in treating MMP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive).

Detailed description: This is a phase 1b, multicenter, feasibility/safety study of the dual delivery (administered through both intracavitary/intratumoral [ICT] and intraventricular [ICV] catheters) of CHM-1101, an autologous chlorotoxin-chimeric antigen receptor (CLTX-CAR) cell product, in participants with recurrent or progressive GBM. The investigational product is identified as CHM-1101 (CLTX(EQ)28ζ/CD19t+ CAR T cells). PRIMARY OBJECTIVE • To determine the recommended phase 2 dose (RP2D) for dual ICT and ICV delivery of CHM-1101 in participants with MMP2+ recurrent or progressive GBM. SECONDARY OBJECTIVES - To assess the feasibility and safety of dual delivery of CHM-1101. - To describe the persistence, expansion, immunogenicity, and phenotype of CHM-1101 and endogenous cells tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF). - In participants who receive at least 2 of the 3 planned doses of CHM-1101 in Cycle 1: - Estimate the progression-free survival (PFS) rates - Estimate the overall survival (OS) rates - To evaluate the disease response rate.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Documented informed consent of the subject and/or legally authorized representative. - Agreement to allow the use of archival tissue from diagnostic tumor biopsies. - Age 18 years and older. - ECOG status of 0 or 1. - Life expectancy ≥12 weeks. - Subject has a prior histologically confirmed diagnosis of a grade 4 glioblastoma multiforme (GBM) or a prior histologically confirmed diagnosis of a grade 2 or 3 malignant glioma and now has radiographic progression consistent with a grade 4 GBM (IDH wild type), grade 4 diffuse astrocytoma (IDH mutant), or has a unifocal relapse of GBM. - Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy and ≥ 12 weeks after completion of front-line radiation therapy. - Confirmed MMP2+ tumor expression by IHC (≥20% moderate/high MMP2 score [2+ or 3+]). - Adequate venous access to perform leukapheresis. - No known contraindications to leukapheresis or steroids. - In-range baseline laboratory values for WBC (>2000/dL [or ANC ≥1000/mm^3]), platelets (≥75000/mm^3), total bilirubin (≤1.5xULN), AST (≤2.5xULN), ALT (≤2.5xULN), serum creatinine (≤1.5xmg/dL), and oxygen saturation (≥95% on room air) - Seronegative for human immunodeficiency virus (HIV) by antigen/antibody (Ag/Ab) testing. - Seronegative for hepatitis B and/or hepatitis C virus. - Women of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. - Agreement by women AND men 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 CHM-1101. (Childbearing potential is defined as not being surgically sterilized (women and men) or, for women, having not been free from menses for > 1 year.) Exclusion Criteria: - Within 3 months of having received prior bevacizumab therapy at the time of enrollment. - Not yet recovered from toxicities of prior therapy. - 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. - Clinically significant uncontrolled illness. - Active infection requiring antibiotics. - Known history of HIV or hepatitis B or hepatitis C infection. - Other active malignancy. - Women 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. - Prospective subjects who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: City of Hope Medical Center

Address:
City: Duarte
Zip: 91010
Country: United States

Facility:
Name: St. David's South Austin Medical Center - Sarah Cannon - Austin

Address:
City: Austin
Zip: 78704
Country: United States

Start date: June 6, 2023

Completion date: January 2041

Lead sponsor:
Agency: Chimeric Therapeutics
Agency class: Industry

Source: Chimeric Therapeutics

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05627323