scholarly journals Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease

Blood ◽  
2018 ◽  
Vol 131 (25) ◽  
pp. 2836-2845 ◽  
Author(s):  
Myrna R. Nahas ◽  
Robert J. Soiffer ◽  
Haesook T. Kim ◽  
Edwin P. Alyea ◽  
Jon Arnason ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Graft Versus Host Disease ◽  
Therapeutic Approach ◽  
Phase 1 ◽  
Phase 1 Clinical Trial ◽  
Graft Versus Host ◽  
Costimulatory Blockade ◽  
Key Points ◽  
Novel Therapeutic ◽  
Steroid Refractory

Key Points Costimulatory blockade using abatacept represents a novel therapeutic approach for the treatment of cGVHD. Abatacept resulted in a clinical response in 44% of patients with both decreased prednisone use and T-cell PD-1 expression in responders.

scholarly journals Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease

Blood ◽  
2017 ◽  
Vol 129 (24) ◽  
pp. 3256-3261 ◽  
Author(s):  
Yi-Bin Chen ◽  
Miguel-Angel Perales ◽  
Shuli Li ◽  
Maria Kempner ◽  
Carol Reynolds ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Multicenter Trial ◽  
Brentuximab Vedotin ◽  
Host Disease ◽  
Graft Versus Host ◽  
Key Points ◽  
Steroid Refractory ◽  
Acute Graft

Key Points BV has activity for SR-aGVHD. The MTD of BV was 0.8 mg/kg every 2 weeks for 4 doses.

scholarly journals Phase 1 study of the Hedgehog pathway inhibitor sonidegib for steroid-refractory chronic graft-versus-host disease

2017 ◽  
Vol 1 (22) ◽  
pp. 1919-1922 ◽  
Author(s):  
Zachariah DeFilipp ◽  
Rosalynn M. Nazarian ◽  
Areej El-Jawahri ◽  
Shuli Li ◽  
Jami Brown ◽  
...  
Keyword(s):  
Adverse Events ◽  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Hedgehog Pathway ◽  
Phase 1 Study ◽  
Graft Versus Host ◽  
Key Points ◽  
Clinical Responses ◽  
Hedgehog Pathway Inhibitor ◽  
Steroid Refractory

Key Points Physician-assessed clinical responses and immunohistochemical changes were seen in association with sonidegib therapy for cGVHD. Sonidegib therapy was limited by ongoing cGVHD symptoms and adverse events not attributed to treatment.

Results of phase 1 clinical trial evaluating efficacy of 3rd party cord blood regulatory T cells for prevention of graft versus host disease.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e15047-e15047
Author(s):  
Joshua Kellner ◽  
Eric Yvon ◽  
Joseph Khoury ◽  
Tuongvan Nguyen ◽  
Jennifer Ramos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cord Blood ◽  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Host Disease ◽  
Phase 1 Clinical Trial ◽  
Graft Versus Host

scholarly journals A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor

Blood ◽  
2014 ◽  
Vol 123 (15) ◽  
pp. 2308-2316 ◽  
Author(s):  
David H. McDermott ◽  
Qian Liu ◽  
Daniel Velez ◽  
Lizbeeth Lopez ◽  
Sandra Anaya-O’Brien ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Low Dose ◽  
Phase 1 ◽  
Cxcr4 Antagonist ◽  
Phase 1 Clinical Trial ◽  
Dose Treatment ◽  
Whim Syndrome ◽  
Key Points

Key Points Plerixafor can be given safely to WHIM syndrome patients twice daily for a 6-month period and appears promising as a treatment.

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1224-1226 ◽  
Author(s):  
Vincent T. Ho ◽  
David Zahrieh ◽  
Ephraim Hochberg ◽  
Eileen Micale ◽  
Jesse Levin ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Interleukin 2 ◽  
Maximum Tolerated Dose ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Denileukin Diftitox ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 μg/kg intravenously on days 1 and 15; 18 received 9 μg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 μg/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (12 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD. (Blood. 2004;104:1224-1226)

scholarly journals Treatment of chronic graft-versus-host disease with bortezomib

Blood ◽  
2014 ◽  
Vol 124 (10) ◽  
pp. 1677-1688 ◽  
Author(s):  
Chien-Chun Steven Pai ◽  
Mingyi Chen ◽  
Annie Mirsoian ◽  
Steven K. Grossenbacher ◽  
Joseph Tellez ◽  
...  
Keyword(s):  
B Cells ◽  
Graft Versus Host Disease ◽  
Germinal Center ◽  
Murine Models ◽  
Host Disease ◽  
Graft Versus Host ◽  
Therapeutic Benefits ◽  
Key Points ◽  
Steroid Refractory ◽  
Germinal Center B Cells

Key Points Bortezomib ameliorates sclerodermatous cGVHD responses by inhibiting germinal center B cells while maintaining GVT effects in murine models. Bortezomib provides therapeutic benefits for patients with active steroid-refractory cGVHD.

scholarly journals Phase I Clinical Trial Evaluating Abatacept in Patients with Steroid-Refractory Chronic Graft Versus Host Disease

2017 ◽  
Vol 23 (3) ◽  
pp. S376
Author(s):  
Myrna R. Nahas ◽  
Robert J. Soiffer ◽  
Edwin P. Alyea ◽  
Jon E. Arnason ◽  
Robin Joyce ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Graft Versus Host Disease ◽  
Phase I Clinical Trial ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory

scholarly journals A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease

2020 ◽  
Vol 4 (8) ◽  
pp. 1656-1669 ◽  
Author(s):  
Mark A. Schroeder ◽  
H. Jean Khoury ◽  
Madan Jagasia ◽  
Haris Ali ◽  
Gary J. Schiller ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Phase 1 ◽  
Janus Kinase ◽  
Open Label ◽  
Major Barrier ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (HCT) is a primary cause of nonrelapse mortality and a major barrier to successful transplant outcomes. Itacitinib is a Janus kinase (JAK)1–selective inhibitor that has demonstrated efficacy in preclinical models of aGVHD. We report results from the first registered study of a JAK inhibitor in patients with aGVHD. This was an open-label phase 1 study enrolling patients aged ≥18 years with first HCT from any source who developed grade IIB to IVD aGVHD. Patients with steroid-naive or steroid-refractory aGVHD were randomized 1:1 to itacitinib 200 mg or 300 mg once daily plus corticosteroids. The primary endpoint was safety and tolerability; day 28 overall response rate (ORR) was the main secondary endpoint. Twenty-nine patients (200 mg, n = 14; 300 mg, n = 15) received ≥1 dose of itacitinib and were included in safety and efficacy assessments. One dose-limiting toxicity was reported (grade 3 thrombocytopenia attributed to GVHD progression in a patient receiving 300 mg itacitinib with preexisting thrombocytopenia). The most common nonhematologic treatment-emergent adverse event was diarrhea (48.3%, n = 14); anemia occurred in 11 patients (38%). ORR on day 28 for all patients in the 200-mg and 300-mg groups was 78.6% and 66.7%, respectively. Day 28 ORR was 75.0% for patients with treatment-naive aGVHD and 70.6% in those with steroid-refractory aGVHD. All patients receiving itacitinib decreased corticosteroid use over time. In summary, itacitinib was well tolerated and demonstrated encouraging efficacy in patients with steroid-naive or steroid-refractory aGVHD, warranting continued clinical investigations. This trial was registered at www.clinicaltrials.gov as #NCT02614612.

scholarly journals Butyrogenic bacteria after acute graft-versus-host disease (GVHD) are associated with the development of steroid-refractory GVHD

2019 ◽  
Vol 3 (19) ◽  
pp. 2866-2869 ◽  
Author(s):  
Jonathan L. Golob ◽  
Martha M. DeMeules ◽  
Tillie Loeffelholz ◽  
Z. Z. Quinn ◽  
Michael K. Dame ◽  
...  
Keyword(s):  
Stem Cells ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Epithelial Monolayer ◽  
Graft Versus Host ◽  
Key Points ◽  
Colonic Stem Cells ◽  
Steroid Refractory ◽  
Acute Graft

Key Points The presence of butyrogenic bacteria after the onset of acute GVHD associates with subsequent steroid-refractory GVHD or chronic GVHD. Butyrate inhibits human colonic stem cells from forming an intact epithelial monolayer.

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