While chimeric antigen receptor T-cell (CAR T-cell) therapy produces impressive response rates in heavily pre-treated patients, early loss of response remains a barrier. One potential mechanism of relapse is limited CAR T-cell persistence. Pre-clinical research shows that PI3K inhibition represents an intriguing mechanism for increasing CAR T-cell persistence that is easily reversible and CAR T-cell agnostic. The investigators hypothesize that PI3K inhibition with duvelisib would be safe, may provide effective prophylaxis against cytokine release syndrome (CRS), and may enhance the persistence and efficacy of CAR T-cells in the treatment of hematologic malignancies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Patients should take duvelisib at approximately the same time every day, with or without food.
CAR T-cells will be given per standard of care.
Washington University School of Medicine
St Louis, Missouri, United States
Toxicity as measured by number of adverse events
Toxicity is graded using NCI CTCAE v 5.0
Time frame: From start of treatment through 30 days after completion of duvelisib (up to day 60 for Cohort A and up to day 212 for Cohort B)
Cumulative incidence of cytokine release syndrome (CRS)
-Any and grade 3-4 per ASTCT criteria
Time frame: By Day 28
Cumulative incidence of immune effector cell-associated neurotoxicity syndrome (ICANS)
-Any and grade 3-4 per ASCT criteria
Time frame: By Day 28
Number of participants who receive anti-IL-6 agents for treatment of cytokine release syndrome (CRS)
Time frame: Through completion of follow-up (estimated to be 6 months)
Number of participants who receive steroids for treatment of cytokine release syndrome (CRS)
Time frame: Through completion of follow-up (estimated to be 6 months)
Number of participants with complete response (CR)
Time frame: At 1 month
Number of participants with complete response (CR)
Time frame: At 3 months
Number of participants with complete response (CR)
Time frame: At 6 months
Best overall response rate
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
Time frame: At 1 month
Best overall response rate
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
Time frame: At 3 months
Best overall response rate
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
Time frame: At 6 months
Progression-free survival (PFS)
Time frame: Through completion of follow-up (estimated to be 5 years)
Overall survival (OS)
Time frame: Through completion of follow-up (estimated to be 5 years)
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 90
Time frame: Day 90
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 180
Time frame: Day 180
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