# A randomized phase 2 trial to compare standard-of-care steroids vs. steroids plus low-dose IL-2 vs. steroids plus low-dose IL-2 and rituximab for upfront treatment of chronic GVHD

> **NIH NIH UG1** · DANA-FARBER CANCER INST · 2020 · $203,233

## Abstract

Project Summary
The promise of marrow transplantation has been diminished by the development of relapse, opportunistic
infection and GVHD. These three complications interlock in a Gordian knot that precludes independent
resolution strategies. Immunologic approaches to relapse result in more GVHD. Conventional pharmacologic
approaches to treat GVHD with increasing immunosuppression result in more opportunistic infection. This is
particularly a concern in non-malignant disease where relapse is less concerning. Our group has adopted an
alternative strategy to treat GVHD, by emphasizing approaches that enhance immunoregulatory networks,
rather than brute force immunosuppression. Our laboratory research has identified several exploitable targets
to control GVHD without global immunosuppression. In this project we focus on chronic GVHD. First, we
specifically expand on our prior work demonstrating that regulatory T cells (Treg) can be selectively expanded
in patients with cGVHD using very low doses of interleukin-2 (IL-2). We demonstrated previously that Treg are
depressed in patients with cGVHD. While infusion of Treg may transiently increase Treg numbers, infusions
are by their nature expensive, time consuming, and logistically complex. Alternatively, Treg can be expanded
in vivo with daily subcutaneous injections that maintain Treg levels at 9-fold above baseline, reverse the ratio
of Treg to conventional CD4+ T cells (Tcon), and ameliorate the manifestations of steroid resistant cGVHD in a
clinically relevant and significant fashion. Moreover, this approach also allows a substantial reduction in
immunosuppressive medications. We hypothesize that expanding Treg at the outset of cGVHD therapy will
allow more effective control of cGVHD manifestations with lower cumulative steroid utilization. Second, we
have demonstrated the critical role of humoral immunity in cGVHD. Basic studies in mice and in humans
indicate that germinal center formation, the development of autologous and allogeneic antibodies, and B cell
cytokines are all important in the generation of cGVHD. Moreover we and others have demonstrated the
benefit of anti-B cell approaches in the therapy (rituximab, ibrutinib) and prophylaxis (rituximab) of cGVHD. We
propose a 3-armed randomized trial comparing the use of the combination of prednisone alone with
prednisone and low dose IL-2, to prednisone, IL-2, and rituximab as primary therapy for cGVHD. The
intermediate goal is to compare the ability of each therapy effectively treat cGVHD. The long-term goal is to
allow us to pick-the-winner for a phase 3 trial and develop an effective, non-toxic, and physiologically relevant
therapy for cGVHD.

## Key facts

- **NIH application ID:** 9934225
- **Project number:** 5UG1HL069249-20
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** JOSEPH H ANTIN
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,233
- **Award type:** 5
- **Project period:** 2001-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934225

## Citation

> US National Institutes of Health, RePORTER application 9934225, A randomized phase 2 trial to compare standard-of-care steroids vs. steroids plus low-dose IL-2 vs. steroids plus low-dose IL-2 and rituximab for upfront treatment of chronic GVHD (5UG1HL069249-20). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9934225. Licensed CC0.

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