# Phase 2 Study of Interferon-Gamma and Donor Lymphocyte Infusion for the Treatment of Relapsed Myeloid Malignancies after Allogeneic Stem Cell Transplantation

> **NIH FDA R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $882,247

## Abstract

Project Summary/Abstract
Allogeneic stem cell transplantation (alloSCT) is a potentially curative therapy for acute myeloid
leukemia (AML) or myelodysplastic syndrome (MDS). Donor-derived alloreactive T cells can kill
recipient leukemia cells, mediating the graft-vs-leukemia effect (GVL). GVL failure leads to post-
transplant relapse, affecting 30-40% of alloSCT recipients and leading to extremely poor
prognosis, with a median survival of 6 months. The clinical sensitivity of leukemias to GVL
varies by disease type. Dr. Shlomchik, Co-PI, sought the mechanism of GVL resistance using
preclinical GVL models and discovered that myeloblastic leukemia required the expression of
the IFN-γ receptor for GVL. Two independent groups reported lower levels of human leukocyte
antigen (HLA) expression in myeloid blasts post-transplant relapse, which IFN-γ can restore in
vitro. These data supported conducting a phase 1 trial to evaluate the safety of IFN-γ
(ACTIMMUNE®) in AML/MDS patients with post-transplant relapse (NCT04628338). 4 out of 6
patients who received IFN-γ and subsequent donor leukocyte infusion (DLI) achieved durable
complete remissions with full donor hematopoiesis recovery. Given these favorable results, we
propose a multicenter phase 2 trial to evaluate the efficacy of IFN-γ/DLI compared to the
outcomes in a synthetic control generated from the Center for International Blood and Marrow
Transplant Research (CIBMTR) database. Patients with AML/MDS who developed relapse with
>5% bone marrow myeloblasts after an HLA-matched alloSCT will be eligible. Subjects will
receive 100mcg of IFN-γ thrice weekly by self-subcutaneous injection for four weeks. If IFN-γ is
tolerated, subjects will receive DLI concurrently with IFN-γ for eight more weeks to complete the
12-week treatment intervention. The primary objective is to evaluate the efficacy of IFN-γ/DLI,
measured by event-free survival at 1 year. The secondary objectives are to evaluate the safety
and efficacy of IFN-γ/DLI measured by secondary endpoints, including measurable disease-
negative complete remission at 6 months and overall survival at 12 months. The incidence of
steroid and ruxolitinib-refractory graft-versus-host disease will be used for the stopping rule. 45
participants will be enrolled to receive IFN-γ/DLI. The major clinical endpoints will be compared
to 3 CIBMTR synthetic cohorts of patients treated with 1) chemotherapy only, 2) chemotherapy+
DLI, or 3) DLI only. Each control group will have 135 subjects (1:3 ratio of treated subjects). In
exploratory studies, we will analyze IFN-γ induced transcriptomic changes in leukemic and
immune cells to find the biomarkers that could be used to select subjects for future studies.

## Key facts

- **NIH application ID:** 11097692
- **Project number:** 1R01FD008187-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sawa Ito
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2024
- **Award amount:** $882,247
- **Award type:** 1
- **Project period:** 2024-09-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11097692

## Citation

> US National Institutes of Health, RePORTER application 11097692, Phase 2 Study of Interferon-Gamma and Donor Lymphocyte Infusion for the Treatment of Relapsed Myeloid Malignancies after Allogeneic Stem Cell Transplantation (1R01FD008187-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11097692. Licensed CC0.

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