Phase I CB-NK-TGF-ßR2-/NR3C1- in rGBM
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12+
SponsorM.D. Anderson Cancer Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Signed and dated informed consent.
Male or female participants aged ≥ 12 years on the day of signing informed consent.
Has histologically confirmed supratentorial World Health Organization grade 4 recurrent astrocytoma to include recurrent IDH WT glioblastoma or gliosarcoma and recurrent IDHmutant grade 4 astrocytoma, and recurrent gliosarcoma with any prior number of recurrences, and who have received prior radiation and temozolomide therapy. Participants will be eligible if the original histology was lower-grade glioma grade 2 or 3 and a subsequent histological diagnosis of recurrent glioblastoma or IDH-mutant grade 4 astrocytoma is made.
Karnofsky Performance Score (KPS) of >70 at trial entry. Lansky >70 at trial entry for patients less than 16.
Disqualifiers
Has received prior therapy with Gliadel or bevacizumab.
Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery.
Is currently participating in or has participated in a study of cancer directed investigational agent or using an investigational device within 4 weeks since last dose of agent administration or device use, or is planning to continue or start treatment with Optune® during participation in this trial.
Has known severe hypersensitivity to monoclonal antibodies, any history of anaphylaxis, or recent, within 5 months, history of uncontrolled asthma.
Trial design
Design model
Sequential
Treatments tested in this trial
Cord Blood-derived Expanded Allogeneic Natural Killer Cells
Biological/VaccineGiven CB-NK-TGF-betaR2-/NR3C1- intratumorally
Resection
Procedure/SurgeryUndergo surgical resection
Treatment groups
25 Participants
are divided into 2 treatment groupsGroup A: Group 1 (CB-NK-TGF-betaR2-/NR3C1- )Experimental treatment 1 intervention
Group B: Group 2 (CB-NK-TGF-betaR2-/NR3C1-, resection)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence of dose-limiting toxicities (DLTs) (Group 1)
Will determine maximum tolerated dose and safety of escalating doses of cord blood (CB)-(NK) cells patients with recurrent glioblastoma. A DLT is defined as any grade \>= 3 adverse event assessed as related to CB-NK cells by the investigator (that is, grade \>= 3 adverse drug reaction; grading according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03.
Time frame
Up to 28 daysSecondary outcomes
1
Overall survival (OS)
OS will be estimated using the Kaplan-Meier method and the comparison between or among patients' characteristics groups will be evaluated by log-rank test. Cox regression models will be applied to assess the effect of covariates of interest on OS.
Time frame
From definitive histological diagnosis until the time of death, assessed up to 90 days post-treatment2
Objective response rate (ORR)
ORR will be defined as the proportion of patients with tumor size reduction (partial response and complete response, per Response Assessment in Neuro-Oncology \[RANO\] criteria). Will be calculated as the ratio of number of patients with response over number of patients treated, and 95% confidence interval of ORR will be estimated.
Time frame
Up to 90 days post-treatment3
Duration of response (DOR)
Time frame
From the time of initial response until documented tumor progression per RANO criteria, assessed up to 90 days4
Time to progression (TTP)
TTP will be estimated using the Kaplan-Meier method and the comparison between or among patients' characteristics groups will be evaluated by log-rank test. Cox regression models will be applied to assess the effect of covariates of interest on TTP.
Time frame
From the date of start of treatment until the tumor progression as defined by RANO, assessed up to 90 days post-treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
M.D. Anderson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov