Center for Medical Ethics and Health Policy Staff Publications
Publication Date
12-1-2022
Journal
Anticancer Research
DOI
10.21873/anticanres.16076
PMID
36456127
PMCID
PMC10132085
PubMedCentral® Posted Date
4-26-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Humans, Receptors, Chimeric Antigen, Immunotherapy, Adoptive, Maximum Tolerated Dose, Clinical Trials, Phase I as Topic, CAR-T, phase I, clinical trial, study design, dose escalation, reporting
Abstract
Background/aim: Chimeric antigen receptor (CAR) T cells with tumor specificity are being increasingly investigated. Phase I trials are the first step of testing for safety of novel CAR-T therapy to determine the maximum tolerated dose (MTD). Several dose escalation methods have been developed over time including rule-based, model-based, and model-assisted designs. The goal of this project is to overview the phase I designs used in current CAR-T trials.
Materials and methods: We searched PubMed for peer-reviewed literature published between January 1, 2015 and December 31, 2021. The search was limited to human studies in the English language using the keywords "CAR-T phase I", "clinical trials", and "full text".
Results: One hundred nine papers with at least partial phase I components were included for analysis. 31.2% of the trials used the traditional 3+3 or a variation of said design, and 60.6% did not mention the dose escalation design. The majority of the manuscripts (59.6%) did not report cohort size while 19.3% did not specify the timing of evaluation. Although most of the studies were registered with CT.gov, only 33.9% had any results submitted or posted to CT.gov These trends persisted even in manuscripts published in journals with high impact factors.
Conclusion: Standardizing the publication criteria and providing basic elements of phase I clinical trials are critical to ensure high quality of manuscripts. With the quick development and high costs of CAR-T cell therapy, adoption of advanced designs such as model-based and model-assisted should increase to improve efficiency of clinical trials.