# Phase III, Multicenter, Randomized, Double-Blind Study of Duvelisib as Cytokine Release Syndrome Prophylaxis in Patients with Large Cell or Mantle Cell Lymphoma Undergoing CAR T-Cell Therapies

> **NIH NIH UG1** · WASHINGTON UNIVERSITY · 2024 · $233,250

## Abstract

PROJECT SUMMARY / ABSTRACT
The Transplant and Cellular Therapy Program at Washington University has been affiliated with the BMT CTN
since its inception, initially as a part of the Case Western Consortium, and as a Core Clinical Center since 2011.
During that time, our institution has made significant contributions to the BMT CTN through clinical trials accrual
and trial design input. The specific purpose of applying for this Notice of Funding Opportunity (NOFO) is to
continue participation as a BMT CTN Core Clinical Center.
The long term goal of the proposed clinical trial is to apply novel concepts in immunology and cellular therapies
to improve outcomes and further expand clinical application of adoptive transgenic chimeric antigen receptor
(CAR) T-cell therapies. While the use of CAR T-cells have emerged as a groundbreaking advancement in the
treatment of many malignant diseases, and has shown a remarkable promise in a variety of non-malignant
disorders, cytokine-release syndrome (CRS) remains a major cause of morbidity and a significant barrier to a
successful outcome. CRS is a hyper-immune reaction driven by excessive inflammatory cytokine activation and
proliferation, with interleukin-6 (IL-6) thought to be one of the most functionally important cytokines during CRS.
Although there are agents used for the treatment of established CRS, including IL-6 antagonist tocilizumab, there
are no FDA-approved agents for CRS prophylaxis. Duvelisib is an oral, dual PI3K-δ,γ inhibitor that is FDA-
approved for the treatment of adults with several hematologic malignancies, with acceptable safety profile. Using
a protein kinase inhibitor library researchers have identified PI3K-δ,γ inhibitors, including duvelisib, as most
potent inhibitors of IL-6 secretion, without attenuating CAR T-cell function. We and others have performed
extensive in vitro and in vivo experiments investigating the effect of duvelisib on CRS cytokines, leading to a
phase I dose escalation and dose expansion study of duvelisib for CRS prophylaxis in patients with non-Hodgkin
lymphomas undergoing CAR T-cell treatments, open for enrollment at Washington University. Preliminary results
from that study show that duvelisib is safe and tolerable, and delays the onset and reduces the severity of CRS.
Based on these data, we propose a phase III, multi-site, randomized, placebo-controlled study with the primary
objective to assess the efficacy of duvelisib in preventing grade ≥2 CRS in patients with large B-cell lymphoma
and mantle cell lymphoma undergoing therapies with axicabtagene ciloleucel, lisocabtagene maraleucel or
brexucabtagene autoleucel (Aim 1). The expected outcome of this trial is to provide definitive data on the
effectiveness of duvelisib for CRS prophylaxis within the study population, without negatively affecting the
efficacy of CAR T-cells. In addition, variety of correlative studies will provide further insight into the biologic
impact of PI3K inhibition, paving the way to ...

## Key facts

- **NIH application ID:** 10938547
- **Project number:** 2UG1HL109137-14
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Iskra Pusic
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,250
- **Award type:** 2
- **Project period:** 2011-08-08 → 2031-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938547

## Citation

> US National Institutes of Health, RePORTER application 10938547, Phase III, Multicenter, Randomized, Double-Blind Study of Duvelisib as Cytokine Release Syndrome Prophylaxis in Patients with Large Cell or Mantle Cell Lymphoma Undergoing CAR T-Cell Therapies (2UG1HL109137-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10938547. Licensed CC0.

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