CARv3-TEAM-E T Cells in Glioblastoma

NCT05660369 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-175
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Glioblastoma; Malignant Glioma; Recurrent Glioblastoma; Recurrent Glioma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AEs)

  Defined as the incidence of ≥ Grade 3-4 adverse events related to CARv3-TEAM-E.

  From Day 0 to 2 years post-treatment

• Number of Dose-Limiting Toxicities (DLTs)

  Defined as any related toxicity experienced by run-in cohort of CTCAE v5 grade ≥ 4 Adverse Event

  up to 6 months

Secondary Outcomes (4)

• Proportion of Participants with One Infusion

  up to 6 months

• Overall Response Rate

  Day 0 to 2 years post-treatment

• Overall Survival Rate

  From Day 0 to 2 years post-treatment

• Progression Free Survival (PFS)

  Registration to 2 years post-treatment

Study Arms (4)

Safety Run-In Phase

EXPERIMENTAL

* Participant enrollment will be staggered by 30 days for up to 3 participants. * Participants will receive 1 infusion of CARv3-TEAM-E. * Phase will be expanded up to 6 participants if any Dose-Limiting Toxicities DLTs occur. * After all participants have been enrolled, there will be an evaluation made by the Data Safety Monitoring Board (DSMB) and the FDA to determine the safety of enrollment into additional arms.

Drug: CARv3-TEAM-E T cells

Arm 1: Recurrent Glioblastoma (GBM), EGFRvIII Positive

EXPERIMENTAL

* Participants will undergo a leukapheresis procedure, or collection of mononuclear T cells via peripheral blood draw. * Rituximab will be administered 5-10 days prior to infusion. * Lymphodepletion chemotherapy treatment will occur 5 days prior to infusion. * CARv3-TEAM-E will be administered via Ommaya on D0 * Participants will be followed for 2 years post-treatment. * Participants who are deriving clinical benefit and have sufficient product can be retreated with up to 5 additional doses.

Drug: CARv3-TEAM-E T cells

Arm 2: Newly Diagnosed GBM, EGFRvIII Positive

EXPERIMENTAL

* Participants will undergo a leukapheresis procedure, or collection of mononuclear T cells via peripheral blood draw. * Rituximab will be administered 5-10 days prior to infusion. * Lymphodepletion chemotherapy treatment will occur 5 days prior to infusion. * CARv3-TEAM-E will be administered via Ommaya on D0 * Participants will be followed for 2 years post-treatment. * Participants who are deriving clinical benefit and have sufficient product can be retreated with up to 5 additional doses.

Drug: CARv3-TEAM-E T cells

Arm 3: Recurrent GBM, EGFRvIII Negative

EXPERIMENTAL

* Participants will undergo a leukapheresis procedure, or collection of mononuclear T cells via peripheral blood draw. * Rituximab will be administered 5-10 days prior to infusion. * Lymphodepletion chemotherapy treatment will occur 5 days prior to infusion. * CARv3-TEAM-E will be administered via Ommaya on D0 * Participants will be followed for 2 years post-treatment. * Participants who are deriving clinical benefit and have sufficient product can be retreated with up to 5 additional doses.

Drug: CARv3-TEAM-E T cells

Interventions

CARv3-TEAM-E T cells DRUG

Autologous T lymphocyte population that contains cells transduced ex-vivo with a CARv3-TEAM-E lentiviral vector encoding a chimeric antigen receptor (CAR). Administered via Ommaya reservoir.

Also known as: Autologous T lymphocyte

Arm 1: Recurrent Glioblastoma (GBM), EGFRvIII Positive; Arm 2: Newly Diagnosed GBM, EGFRvIII Positive; Arm 3: Recurrent GBM, EGFRvIII Negative; Safety Run-In Phase

Eligibility Criteria

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

You may qualify if:

• Safety Run In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant
• Participants must have histologically confirmed recurrent GBM or molecular features of GBM with presence of EGFRvIII mutation detected at initial diagnosis. MGMT methylated, unmethylated, or unknown is allowed.
• Participants must be at first progression or recurrence and plan is for biopsy or surgical debulking. Participants must have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.
• Participants must be 2 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent before proceeding with collection or treatment. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.
• ARM 2: Newly Diagnosed GBM, EGFRvIII mutant (will only open once safety is confirmed in Arms 1 and 3)
• 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
• Participants must have histologically confirmed recurrent GBM with EGFR amplification but no EGFRvIII mutation based on initial diagnostic tissue.
• Participants must be at first recurrence and plan is for biopsy or surgical debulking. Participants must have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.
• Participants must be 2 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.
• ARM 1: Recurrent GBM, EGFRvIII mutant and ARM 3: Recurrent GBM, EGFRvIII negative:
• Must be at least 3 months from completion of radiation or evidence of progression is outside the high dose radiation field.
• Safety Run-In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant and ARM 3: Recurrent GBM, EGFRvIII negative:
• Participants must have measurable disease, defined as at least one lesion ≥10 mm (≥1 cm) with MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.

You may not qualify if:

• Intraparenchymal posterior fossa disease
• Intramedullary spinal disease as the only site of disease.
• Prior EGFRvIII targeted therapies.
• Prior bevacizumab treatment.
• Treatment with an any prior gene-therapy or gene-modified cellular therapy.
• Patients with a VP shunt or patients needing a shunt in the immediate future are excluded from participating
• 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.

Sponsors & Collaborators

• Marcela V. Maus, M.D.,Ph.D.: lead

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02215, United States

RECRUITING

Related Publications (1)

• Choi BD, Gerstner ER, Frigault MJ, Leick MB, Mount CW, Balaj L, Nikiforow S, Carter BS, Curry WT, Gallagher K, Maus MV. Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma. N Engl J Med. 2024 Apr 11;390(14):1290-1298. doi: 10.1056/NEJMoa2314390. Epub 2024 Mar 13.

  PMID: 38477966 DERIVED

MeSH Terms

Conditions

Glioblastoma; Glioma

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

Study Officials

• William Curry, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William Curry, MD

CONTACT

617-724-6226; carteamingbm@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: December 21, 2022
• Study Start: March 22, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)