# Ustekinumab for Graft versus Host Disease Prevention (IND 144540)

> **NIH FDA R01** · FRED HUTCHINSON CANCER CENTER · 2020 · $488,317

## Abstract

PROJECT SUMMARY
Current standard immune suppression (IS) prophylaxis delivered after allogeneic hematopoietic cell
transplantation (HCT) fails to effectively prevent graft vs. host disease (GVHD) after HCT. Importantly, GVHD
leads to HCT-associated morbidity, death, and impaired quality of life. Recipients of unrelated donor HCT are
in particular need given excess GVHD risk, and investigational strategies tailored to these patients are urgently
needed. Our experimental and clinical trial data support that selective IL-12/23p40 neutralization is a rational
and targeted approach to prevent GVHD: In murine systems, we demonstrate that IL-12 blockade prevents
GVHD. In an initial proof of concept trial clinical trial, we demonstrated that IL-12/23p40 neutralization with the
agent ustekinumab safely prolonged time to acute GVHD onset, improved grade II-IV acute GVHD-free
survival, decreased Th1 and Th17 cell responses, decreased REG3a (a blood biomarker of GVHD lethality),
and significantly improved overall survival and CRFS (chronic GVHD-, relapse-free survival). Building from
these data, we now propose a randomized, double-blinded, placebo-controlled phase II trial to determine if
ustekinumab therapy vs. placebo (both given with standard pharmacologic immune suppression prophylaxis)
improves 6 month grade II-IV acute GVHD-free survival. Secondary endpoints will fully assess risk/benefit of
the study intervention, chronic GVHD outcomes through 2 years post-HCT, and patient-reported symptom
burden and QOL. We will also discern the biologic impact of this intervention on human immunity after HCT
through comprehensive studies. In total, the proposal has major potential to advance the research field of
transplantation, and enhance safe HCT utilization for treatment of hematological malignancies and disorders.

## Key facts

- **NIH application ID:** 10644318
- **Project number:** 6R01FD006836-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** STEPHANIE J LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $488,317
- **Award type:** 6
- **Project period:** 2020-08-24 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10644318

## Citation

> US National Institutes of Health, RePORTER application 10644318, Ustekinumab for Graft versus Host Disease Prevention (IND 144540) (6R01FD006836-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10644318. Licensed CC0.

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