RECRUITING

CARv3-TEAM-E T Cells in Glioblastoma

Conditions

Glioblastoma Malignant Glioma Recurrent Glioblastoma Recurrent Glioma Immunotherapy Gene-Transfer Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The goal of this research study is to determine the best dose of CARv3-TEAM-E T Cells for treating participants with glioblastoma. The name of the treatment intervention used in this research study is: -CARv3-TEAM-E T Cells (or Autologous T lymphocytes).

Official Title

INCIPIENT: INtraventricular CARv3-TEAM-E T Cells for PatIENTs With GBM

Quick Facts

Study Start:2023-03-22

Study Completion:2026-06-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05660369

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Participants must have histologically confirmed recurrent GBM or molecular features of GBM with presence of EGFRvIII mutation within 30 days of consent. MGMT methylated, unmethylated, or unknown is allowed. * Participants must be at first progression or recurrence and have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated. * ARM 2: Newly Diagnosed GBM, EGFRvIII mutant * Participants must have histologically confirmed newly diagnosed GBM with presence of EGFRvIII mutation and their tumors must be MGMT unmethylated. * Treatment planned with involved field radiation alone without concomitant or sequential temozolomide. * ARM 3: Recurrent GBM, EGFRvIII negative (will only open once safety is confirmed in Arms 1 and 2) * Participants must have histologically confirmed recurrent GBM with absence of EGFRvIII mutation within 30 days of consent but with EGFR amplification. * Participants must be at first recurrence and have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated. Participants must be 4 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent. No washout is required from radiation since participants will need histological confirmation of recurrence to participate. * ALL ARMS: * Participants must have measurable disease, defined as at least one lesion ≥10 mm (≥1 cm) with MRI. Patients cannot have posterior fossa or intramedullary spine-only disease. Leptomeningeal disease is allowed anywhere in the neuroaxis. See Section 11 (Measurement of Effect) for the evaluation of measurable disease. * Resolution of AEs from any prior systemic anticancer therapy or radiotherapy to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy) * Medically able and willing to undergo placement of an Ommaya reservoir. * Steroid dose anticipated to be ≤ 4 mg of dexamethasone a day or equivalent at time of first CAR-v3-TEAM-E infusion. * Age ≥18 years * Karnofsky ≥60% (see Appendix A). * Must be able to undergo an MRI with contrast. * Life expectancy of greater than 3 months. * Participants must have adequate organ and marrow function as defined below: * absolute neutrophil count ≥1,000/mcL * platelets ≥80,000/mcL * total bilirubin ≤ institutional upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN * creatinine ≤ institutional ULN OR * glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 * Participant has no prior history of malignancy, unless the subject has been free of the disease for ≥5 years with the exception of the following noninvasive malignancies: * Basal cell carcinoma of the skin * Squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T1a or T1b) or prostate cancer that is curative * Left ventricular ejection fraction \>50% as determined by TTE. * The effects of CARv3-TEAM-E on the developing human 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; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CARv3-TEAM-E administration. * Ability to understand and the willingness to sign a written informed consent document.	* Intraparenchymal posterior fossa disease * Intramedullary spinal disease as the only site of disease. * Prior EGFRvIII targeted therapies. * Treatment with an any prior gene-therapy or gene-modified cellular therapy. * Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids above physiologic dosing). Intermittent topical, inhaled, or intranasal corticosteroids are allowed * Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia. * Participants who are receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to CARv3-TEAM-E (ex. cetuximab). * Participants with uncontrolled intercurrent illness. * Human immunodeficiency virus (HIV)-infected participants are not eligible. * Participants with evidence of chronic hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection are not eligible. * Participants with psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CARv3-TEAM-E , breastfeeding should be discontinued if the mother is treated with CARv3-TEAM-E. * For Arm 2, prior to CARv3-TEAM-E Infusion, the following criteria should be confirmed in addition to the relevant criteria above: * Participants must have completed 75% of the planned 6 weeks of involved field radiation without temozolomide * Tumor location and size criteria as in 3.1.7 above. * Prior cancer directed therapy other than radiation is not allowed.

Inclusion Criteria

Exclusion Criteria

* Participants must have histologically confirmed recurrent GBM or molecular features of GBM with presence of EGFRvIII mutation within 30 days of consent. MGMT methylated, unmethylated, or unknown is allowed.
* Participants must be at first progression or recurrence and have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.
* ARM 2: Newly Diagnosed GBM, EGFRvIII mutant
* Participants must have histologically confirmed newly diagnosed GBM with presence of EGFRvIII mutation and their tumors must be MGMT unmethylated.
* Treatment planned with involved field radiation alone without concomitant or sequential temozolomide.
* ARM 3: Recurrent GBM, EGFRvIII negative (will only open once safety is confirmed in Arms 1 and 2)
* Participants must have histologically confirmed recurrent GBM with absence of EGFRvIII mutation within 30 days of consent but with EGFR amplification.
* Participants must be at first recurrence and have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated. Participants must be 4 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.
* ALL ARMS:
* Participants must have measurable disease, defined as at least one lesion ≥10 mm (≥1 cm) with MRI. Patients cannot have posterior fossa or intramedullary spine-only disease. Leptomeningeal disease is allowed anywhere in the neuroaxis. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
* Resolution of AEs from any prior systemic anticancer therapy or radiotherapy to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy)
* Medically able and willing to undergo placement of an Ommaya reservoir.
* Steroid dose anticipated to be ≤ 4 mg of dexamethasone a day or equivalent at time of first CAR-v3-TEAM-E infusion.
* Age ≥18 years
* Karnofsky ≥60% (see Appendix A).
* Must be able to undergo an MRI with contrast.
* Life expectancy of greater than 3 months.
* Participants must have adequate organ and marrow function as defined below:
* absolute neutrophil count ≥1,000/mcL
* platelets ≥80,000/mcL
* total bilirubin ≤ institutional upper limit of normal (ULN)
* AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
* creatinine ≤ institutional ULN OR
* glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2
* Participant has no prior history of malignancy, unless the subject has been free of the disease for ≥5 years with the exception of the following noninvasive malignancies:
* Basal cell carcinoma of the skin
* Squamous cell carcinoma of the skin
* Carcinoma in situ of the cervix
* Carcinoma in situ of the breast
* Incidental histologic finding of prostate cancer (T1a or T1b) or prostate cancer that is curative
* Left ventricular ejection fraction \>50% as determined by TTE.
* The effects of CARv3-TEAM-E on the developing human 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; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CARv3-TEAM-E administration.
* Ability to understand and the willingness to sign a written informed consent document.

* Intraparenchymal posterior fossa disease
* Intramedullary spinal disease as the only site of disease.
* Prior EGFRvIII targeted therapies.
* Treatment with an any prior gene-therapy or gene-modified cellular therapy.
* Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids above physiologic dosing). Intermittent topical, inhaled, or intranasal corticosteroids are allowed
* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
* Participants who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CARv3-TEAM-E (ex. cetuximab).
* Participants with uncontrolled intercurrent illness.
* Human immunodeficiency virus (HIV)-infected participants are not eligible.
* Participants with evidence of chronic hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection are not eligible.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CARv3-TEAM-E , breastfeeding should be discontinued if the mother is treated with CARv3-TEAM-E.
* For Arm 2, prior to CARv3-TEAM-E Infusion, the following criteria should be confirmed in addition to the relevant criteria above:
* Participants must have completed 75% of the planned 6 weeks of involved field radiation without temozolomide
* Tumor location and size criteria as in 3.1.7 above.
* Prior cancer directed therapy other than radiation is not allowed.

Contacts and Locations

Study Contact

William Curry, MD

CONTACT

617-724-6226

carteamingbm@mgb.org

Principal Investigator

William Curry, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

Sponsor: Marcela V. Maus, M.D.,Ph.D.

William Curry, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-22

Study Completion Date2026-06-01

Study Record Updates

Study Start Date2023-03-22

Study Completion Date2026-06-01

Terms related to this study

Keywords Provided by Researchers

Glioblastoma
Malignant Glioma
Recurrent Glioblastoma
Recurrent Glioma
Immunotherapy
Gene-Transfer Therapy

Additional Relevant MeSH Terms

Glioblastoma
Malignant Glioma
Recurrent Glioblastoma
Recurrent Glioma