Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Arm 1 participants will undergo resection of their tumor. Participants receive half the CHM-1101 dose via Rickham catheters into the tumor cavity and half into the lateral ventricle.

Cycle 1 (28 days) CHM 1101 total dose will be divided across 3 once-weekly administrations.

After Cycle 1, additional cycles may be initiated in the absence of disease progression or unacceptable toxicity provided that the principal investigator and participant agree to continue and if adequate autologous CAR-T doses remain.

Arm 2 participants will undergo resection of their tumor. Participants receive half the CHM-1101 dose via Rickham catheters into the tumor cavity and half into the lateral ventricle.

Cycle 1 (28 days) CHM 1101 total dose will be divided across 3 once-weekly administrations.

After Cycle 1, additional cycles may be initiated in the absence of disease progression or unacceptable toxicity provided that the principal investigator and participant agree to continue and if adequate autologous CAR-T doses remain.

CHM-1101 CAR-T cells

Chimeric Therapeutics

Cara Nolan

Behnam Badie

Aravind Ramakrishnan, MD

Jason Litten, MD

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).

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.

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.

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

A Phase 1b Study to Evaluate CHM-1101, a CAR T-Cell Therapy With a Chlorotoxin Tumor-Targeting Domain for Patients With Matrix Metallopeptidase 2 Positive (MMP2+) Recurrent or Progressive Glioblastoma Multiforme

Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Assessed per American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading guideline, evaluating levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry).

Assess levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry).

Assess level and phenotype detected in TCF, PB, and CSF (absolute number per µL by flowcytometry).

Serum samples will be evaluated for HACA against the CLTX(EQ)28ζ therapeutic agent.

Measured from the date of first infusion of CAR-T cells until the first date when progressive disease (PD) is objectively documented or death from any cause, whichever is earlier.

Measured from the date of first infusion of CAR-T cells until death.

Assessed by modified Response Assessment in Neuro-Oncology Criteria (RANO) criteria.

The proportion of participants who experience a complete response, a partial response, or stable disease that is 3 months or greater in duration.

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

One week on temozolomide is followed by a week without temozolomide.

Temozolomide is given over 3 weeks, followed by a week without temozolomide.

Temozolomide in both arms

Michael Weller, Prof. Dr.

For patients with progressive or recurrent glioblastoma there is no standard therapy. One strategy is re-exposure to temozolomide in a higher dose. This increase in dosing can be done by 2 regimens. Aim of this study is to compare these 2 dosing regimens concerning toxicity. In study arm A patients receive temozolomide for one week, followed by a week without temozolomide. In study arm B patients receive temozolomide for three weeks, followed by a week without temozolomide. The regimen that is less toxic will be selected for further evaluations.

Comparison of Two Dosing Regimens of Temozolomide in Patients With Progressive or Recurrent Glioblastoma

Dose-intensified Rechallenge With Temozolomide, One Week On One Week Off Versus Three Weeks On One Week Off in Patients With Progressive or Recurrent Glioblastoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CAR T Cells in Patients With MMP2+ Recurrent or Progressive Glioblastoma	NCT05627323	Glioblastoma Mu...	CHM-1101 CAR-T ...	18 Years -	Chimeric Therapeutics
Comparison of Two Dosing Regimens of Temozolomide in Patients With Progressive or Recurrent Glioblastoma	NCT00941460	Glioblastoma	Temozolomide in... Temozolomide in...	18 Years - 80 Years	Heidelberg University
CAR T Cells in Patients With MMP2+ Recurrent or Progressive Glioblastoma	NCT05627323	Glioblastoma Mu...	CHM-1101 CAR-T ...	18 Years -	Chimeric Therapeutics

Spots Global Cancer Trial Database for progressive or recurrent glioblastoma