Status and phase
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About
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).
Full description
This is a non-randomized, open label, single site Phase 1 study to define the appropriate dose of CARv3-TEAM-E and evaluate its safety for the treatment of recurrent or newly diagnosed glioblastoma.
The U.S. Food and Drug Administration (FDA) has not approved CARv3-TEAM-E T Cells as a treatment for any disease. This is the first time that CARv3-TEAM-E T Cells will be given to humans. CARv3-TEAM-E T Cells are made from a person's own collected immune cells (T-Cells) that are genetically changed and then delivered back into the body to try to kill their cancerous cells.
The research study procedures include screening for eligibility, study treatment, including evaluations and follow up visits, blood collections, echocardiograms, and radiologic imaging of tumors.
It is expected participants will receive treatment over a period of short-term (approx. 2 years) and then long-term follow-up of up to 15 years.
It is expected that about 21 people will take part in this research study.
This research study has received funding through an internal grant program.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Safety Run In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant
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)
ARM 3: Recurrent GBM, EGFRvIII negative
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:
Safety Run-In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant and ARM 3: Recurrent GBM, EGFRvIII negative:
ALL ARMS:
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%
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:
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:
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.
Exclusion criteria
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.
For Arm 2, prior to CARv3-TEAM-E Infusion, the following criteria should be confirmed in addition to the relevant criteria above:
Primary purpose
Allocation
Interventional model
Masking
21 participants in 4 patient groups
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Central trial contact
William Curry, MD
Data sourced from clinicaltrials.gov
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