Engineered NK Cells Containing Deleted TGF-BetaR2 & NR3C1 for

Status Recruiting

Clinical Trial Summary

This phase I trial is to find out the best dose, possible benefits and/or side effects of engineered natural killer (NK) cells containing deleted TGF-betaR2 and NR3C1 (cord blood [CB]-NK-TGF-betaR2-/NR3C1-) in treating patients with glioblastoma that has come back (recurrent). CB-NK-TGF-betaR2-/NR3C1- cells are genetically changed immune cells that may help to control the disease.

Clinical Trial Description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of escalating doses of off-the-shelf CB-NK-TGF-betaR2-/NR3C1- in patients with recurrent glioblastoma (GBM), occurrence of dose limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD). (Group 1) II. To evaluate the immunological phenotype and anti-tumor function of NK cells in resected tumor tissue after treatment with CB-NK-TGF-betaR2-/NR3C1- in the surgical expansion group. (Group 2) SECONDARY OBJECTIVE: I. To determine response as measured by Response Assessment in Neuro-Oncology (RANO), duration of clinical response, progression free survival (PFS), time to progression (TTP), and overall survival (OS). EXPLORATORY OBJECTIVES: I. Monitoring immune responses following CB-NK-TGF-betaR2-/NR3C1- dosing, in vivo persistence and expansion of CB-NK-TGF-betaR2-/NR3C1- during treatment, characterization of immune cell subpopulations in the peripheral blood, serum analysis of immune correlates, alloreactivity characterization, and anti-HLA antibody analysis, and CB-NK-TGF-betaR2-/NR3C1- trafficking in tumor microenvironments in the surgical expansion cohort. II. Tumor tissue from surgical resection will be further analyzed for immune infiltrates, fibrosis, and tumor microenvironment. OUTLINE: This is a dose-escalation study followed by a dose-expansion study. Patients are assigned to 1 of 2 groups. GROUP 1: Patients receive CB-NK-TGF-betaR2-/NR3C1- intratumorally over 5-10 minutes weekly for up to 8 doses in the absence of disease progression or unacceptable toxicity. GROUP 2: Patients receive CB-NK-TGF-betaR2-/NR3C1- intratumorally over 5-10 minutes on days 0, 7, and 14. Patients undergo standard of care surgical resection on day 15. Beginning 2 weeks after surgery, patients receive CB-NK-TGF-betaR2-/NR3C1- intratumorally over 5-10 minutes weekly for up to 5 doses (total of 8 doses) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 7, 30, and 90 days. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT04991870
Study type	Interventional
Source	M.D. Anderson Cancer Center
Contact	Shiao-Pei Weathers, MD
Phone	713-792-2883
Email	sweathers@mdanderson.org
Status	Recruiting
Phase	Phase 1
Start date	April 28, 2023
Completion date	January 31, 2025

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See also
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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Engineered NK Cells Containing Deleted TGF-BetaR2 and NR3C1 for the Treatment of Recurrent Glioblastoma

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms