Memory-Enriched T Cells in Treating Patients With Recurrent or Refractory Grade III-IV Glioma

NCT03389230 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 16064NCI-2017-01755P30CA033572
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of memory-enriched T cells in treating patients with grade II-IV glioma that has come back (recurrent) or does not respond to treatment (refractory). Memory enriched T cells such as HER2(EQ)BBζ/CD19t+ T cells may enter and express its genes in immune cells. Immune cells can be engineered to kill glioma cells in the laboratory by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells that allows them to recognize glioma cells. A vector called lentivirus is used to carry the piece of DNA into the immune cell. It is not known whether these immune cells will kill glioma tumor cells when given to patients.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Incidence of grade 3 adverse events

  Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity and arm.

  Up to 3 years

• Dose limiting toxicities (DLT)

  Rate and associated 90% Clopper and Pearson binomial confidence limits (90% confidence interval \[CI\]) will be estimated for participants' experiencing DLTs at the recommended phase 2 dose (RP2D) schedule.

  Up to 3 years

• Incidence of adverse events

  Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity and arm.

  Up to 3 years

Secondary Outcomes (7)

• Chimeric antigen receptor (CAR) T cells detected in tumor cyst fluid, peripheral blood, and cerebrospinal fluid (CSF)

  Up to 3 years

• Tumor cyst fluid, peripheral blood, and cerebrospinal fluid (CSF) cytokine levels

  Up to 3 years

• Progression free survival

  At 6 months

• Overall Survival (OS)

  At 6 months

• Disease response

  Up to 3 years

Study Arms (3)

Arm I (intratumoral/intracavitary delivery)

EXPERIMENTAL

Patients receive autologous HER2(EQ)BBzeta/CD19t+ Tcm cells via intratumoral/intracavitary catheter over 5 minutes weekly for 3 weeks. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients remain eligible and there is product available. Patients who progress on intracavitary or intratumoral administration may move to alternative delivery routes for the optional infusions.

Biological: HER2(EQ)BBζ/CD19t+ T cells; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis

Arm II (dual delivery Tcm enriched)

EXPERIMENTAL

Patients receive autologous HER2(EQ)BBzeta/CD19t+ Tcm cells via intratumoral/intracavitary catheter and intraventricular catheter over 5 minutes weekly for 3 weeks. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites).

Biological: HER2(EQ)BBζ/CD19t+ T cells; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis

ARM III (dual delivery Tn/mem enriched)

EXPERIMENTAL

Patients receive autologous HER2(EQ)BBzeta/CD19t+ Tn/mem cells via intratumoral/intracavitary catheter and intraventricular catheter over 5 minutes weekly for 3 weeks. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites).

Biological: HER2(EQ)BBζ/CD19t+ T cells; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis

Interventions

HER2(EQ)BBζ/CD19t+ T cells BIOLOGICAL

Given via catheter

ARM III (dual delivery Tn/mem enriched); Arm I (intratumoral/intracavitary delivery); Arm II (dual delivery Tcm enriched)

Laboratory Biomarker Analysis OTHER

Correlative studies

ARM III (dual delivery Tn/mem enriched); Arm I (intratumoral/intracavitary delivery); Arm II (dual delivery Tcm enriched)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

ARM III (dual delivery Tn/mem enriched); Arm I (intratumoral/intracavitary delivery); Arm II (dual delivery Tcm enriched)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has a prior histologically-confirmed diagnosis of a grade III or IV glioma, or has a prior histologically-confirmed diagnosis of a grade II glioma and now has radiographic progression consistent with a grade III or IV malignant glioma (MG)
• Karnofsky performance status (KPS) \>= 60%
• Life expectancy \> 4 weeks
• The effects of HER2(EQBBzeta/CD19t+ T cells on the developing fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• City of Hope (COH) Clinical Pathology confirms HER2+ tumor expression by immunohistochemistry (\>= 20%, 1+)
• All research participants must have the ability to understand and the willingness to sign a written informed consent
• 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 full consent is processed; however, the research participant is allowed to proceed with rickham placement and CAR T cell infusion only after the translated full consent form is signed
• ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) COLLECTION
• Research participant must not require more than 2 mg three times daily (TID) of dexamethasone on the day of PBMC collection.
• Research participant must have appropriate venous access
• At least 2 weeks must have elapsed since the research participant received his/her last dose of prior targeted agents, chemotherapy or radiation; at the principal investigator's discretion, exception can be made for investigational agents that are delivered locally into the CSF
• ELIGIBILITY TO PROCEED WITH RICKHAM PLACEMENT
• Once research participants meet eligibility to proceed with Rickham placement, they will be deemed accrued on to the study
• Note: if the participant had received prior targeted radiation and new lesions have appeared outside of that targeted area, then that may be deemed radiographic evidence of measurable disease even if 12 weeks have not elapsed
• Creatinine \< 1.6 mg/dL

You may not qualify if:

• Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
• Research participants with a known history of congestive heart failure (CHF) or cardiac symptoms consistent with New York Heart Association (NYHA) classification III-IV within 6 months prior to Day 1 of protocol treatment, cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic medications or with clinical history suggestive of the above must have an electrocardiogram (EKG) and echocardiogram (ECHO) performed within 42 days prior to registration and as clinically indicated while on treatment
• Research participants with new symptoms of CHF, cardiomyopathy, myocarditis, MI, or exposure to cardiotoxic medications must have a cardiac consultation, creatinine phosphokinase (CPK), and troponin testing at pre -study and as clinically indicated
• Research participant requires dialysis
• Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
• Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
• Research participants with any other active malignancies
• Research participants being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator
• Research participants with any uncontrolled illness including ongoing or active infection; research participants with known active hepatitis B or C infection; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
• Research participants who have confirmed human immunodeficiency virus (HIV) positivity within 4 weeks of enrollment

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

Leukapheresis

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

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2017
• First Posted: January 3, 2018
• Study Start: August 14, 2018
• Primary Completion (Estimated): December 29, 2026
• Study Completion (Estimated): December 29, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-02

Locations

US (1)