GPC3 CAR T Cells With IL-15 and IL-21 for Recurrent ATRT and CNS Rhabdoid Tumors (RADIANT)
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age1-21
SponsorBaylor College of Medicine
About this trial
This study is being conducted in patients with GPC3-positive brain tumors that have recurred or have not responded to standard therapy. Atypical teratoid rhabdoid tumors (ATRT) are aggressive tumors with poor outcomes and limited treatment options, particularly in young children. There is a need for new therapies that can improve outcomes while minimizing toxicity.
This study evaluates a new experimental treatment using genetically engineered T cells (RADIANT-T cells) that target glypican-3 (GPC3), a protein expressed on tumor cells. These T cells are modified to express a chimeric antigen receptor (CAR) targeting GPC3, along with IL-15 and IL-21 to enhance their persistence and activity. The cells also include an inducible safety mechanism (iCasp9) that allows them to be eliminated if necessary.
The purpose of this study is to determine the highest safe dose of RADIANT-T cells, evaluate their safety and side effects, assess how long they persist in the body, and determine whether they show anti-tumor activity in patients with GPC3-positive brain tumors.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1) Diagnosis of GPC3-positive recurrent ATRT.
2) Age ≥ 6 months
3) Karnofsky/Lansky score ≥ 60%
4) Informed consent explained to, understood by, and signed by patient/guardian; copy provided
Disqualifiers
1) No history of organ transplantation
2) No known HIV positivity
3) No active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
4) No other risk factors in which administration of the investigational agent is deemed not in the patient's best interest, in the opinion of the investigator
Trial design
Design model
Single group
Treatments tested in this trial
21.15.GPC3-CAR T Cells
Biological/VaccineAutologous T cells genetically engineered using retroviral vectors encoding a GPC3-specific CAR and IL-15 and IL-21 cytokines. The product also includes an inducible caspase-9 safety switch allowing pharmacologic elimination of the CAR T cells in the event of severe toxicity.
Treatment groups
21 Participants
are divided into 1 treatment groupGroup A: Treatment with 21.15.GPC3-CAR T Cell Therapy (RADIANT CAR T Cells)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of Participants with Dose-Limiting Toxicity
DLT will be defined as any of the following that may be considered possibly, probably, or definitely related to the 21.15.GPC3-CAR T cells: Any Grade 5 event, Non-hematologic dose-limiting toxicity (any Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours), Grade 4 allergic reaction to CAR T cell administration, Grade 4 reactions due to CRS and neurotoxicity (rarely seen with the use of CAR-based immunotherapy), Grade 3 cytokine release syndrome (CRS) infusion reactions and neurologic toxicity that fail to return to Grade 1 within 72 hours, Grade 4 CRS and neurologic toxicities
Time frame
4 weeks after CAR T-cell administrationSecondary outcomes
1
Maximum Tolerated Dose (MTD) of intratumoral and/or ICV injection of 21.15.GPC3-CAR T cells in treating patients with GPC3-positive recurrent or incompletely resected ATRT.
Once dose escalation is finished and all patients are evaluable for DLT, we will determine the MTD based on isotonic regression, specifically, the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there is no DLT that determine a MTD, the maximum dose level will be declared as the MTD. In case the lowest dose level is determined to be too toxic and the elimination boundary is reached, no MTD will be defined for the trial.
Time frame
28 days2
Response Rate
Response rates will be estimated as the percent of patients whose best response is either complete response or partial response by combining the data from lesions recorded via imaging for each patient pre- and post- 21.15.GPC3-CAR T-cell intratumoral and/or ICV injection. Per immunotherapy response assessment for neuro-oncology (iRANO) criteria: * Complete Response (CR): Disappearance of all enhancing disease for ≥4 weeks; no new lesions; stable or improved T2/FLAIR; no more than physiological steroids; clinically stable or improved. * Partial Response (PR): ≥50% decrease in the sum of biperpendicular diameters of enhancing disease for ≥4 weeks; no new lesions; stable or improved T2/FLAIR; stable or decreased steroid dose; clinically stable or improved.
Time frame
4-6 weeks after CAR T-cell administrationSponsors and contacts
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Source ClinicalTrials.gov
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