Phase 1/2 study of high-dose palifermin for GVHD prophylaxis in patients undergoing HLA-matched unrelated donor HCT
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). Palifermin, a recombinant N-truncated keratinocyte growth factor (KGF), protects epithelial tissues, including the thymus and gut. Although high-dose KGF prevents GVHD in preclinical models, lower doses of palifermin were ineffective in humans. We conducted a phase 1/2 trial evaluating high-dose palifermin for preventing severe chronic GVHD (CGVHD) in matched unrelated donor T-cell replete peripheral blood HCT after reduced-intensity conditioning (RIC). Using a 3+3 design, we determined the recommended phase 2 dose (RP2D), followed by an expansion phase. Palifermin (180-720 μg/kg) was given on day -7 before HCT. All 31 patients received fludarabine/cyclophosphamide RIC with tacrolimus, methotrexate, and sirolimus for GVHD prophylaxis. Palifermin was well tolerated, with self-limiting rash and pancreatic enzyme elevations as notable grade 3/4 adverse events. The RP2D was 720 μg/kg. Remarkably, no patients at this dose developed grade 2 to 4 acute GVHD (AGVHD [0/19]), although severe CGVHD rates (primary end point) remained unchanged compared to historical controls. Posttransplant lymphocyte phenotyping suggests palifermin modulates regulatory and naïve CD4+ T-cell numbers. These findings indicate that high-dose palifermin with RIC is safe and may prevent AGVHD, although it did not affect CGVHD rates in this study. This trial was registered at www.ClinicalTrials.gov as #NCT02356159.
Source: Blood
Authors: Eduard Schulz, Lauren M. Curtis, Noa G. Holtzman, Seth M. Steinberg, Kaska Wloka, Alen Ostojic, Alain Mina, Najla El Jurdi, Filip Pirsl, Ashley Carpenter, Mahshid Golagha, Arlene Sirajuddin, Theo Heller, Brian C. Shaffer, Frances T. Hakim, Jeffrey S. Rubin, Ronald E. Gress, Steven Z. Pavletic
Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research, Mount Auburn Hospital, Harvard University, Sylvester Comprehensive Cancer Center, National Institutes of Health Clinical Center, National Institute of Diabetes and Digestive and Kidney Diseases, Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4410160036