Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis

Koji Sasaki, Jason R. Gotlib, Ruben A. Mesa, Kate J. Newberry, Farhad Ravandi, Jorge E. Cortes, Patrick Kelly, Jeffery L. Kutok, Hagop M. Kantarjian, Srdan Verstovsek

Research output: Contribution to journalArticle

Abstract

The clinical safety and efficacy of IPI-926 was evaluated in 14 patients with myelofibrosis in a phase II study. Patients received 160 mg IPI-926 orally in continuous 28-day cycles. The median treatment duration was 5.1 months, and all patients had discontinued treatment by 7.5 months. Nine patients discontinued due to lack of response as determined by the treating physician, two after developing acute leukemia and one due to disease progression/loss of response. Twelve patients had slight reductions in spleen size (less than 50% from baseline), but symptoms did not improve consistently. One patient achieved transfusion independence lasting 5 months. Reductions in GLI1 mRNA and protein levels, JAK2V617F allele burden, degree of fibrosis or cytokine levels were observed in some patients, but were not significant when evaluated for the cohort. Low-grade gastrointestinal/liver abnormalities were the most common toxicities. The results did not support continued evaluation of IPI-926 as a monotherapy in myelofibrosis.

Original languageEnglish (US)
Pages (from-to)2092-2097
Number of pages6
JournalLeukemia and Lymphoma
Volume56
Issue number7
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

Fingerprint

Primary Myelofibrosis
IPI-926
Disease Progression
Leukemia
Fibrosis
Spleen
Alleles
Cytokines
Physicians
Safety
Messenger RNA
Liver
Therapeutics

Keywords

  • Hedgehog inhibitor
  • IPI-926
  • Myelofibrosis
  • Saridegib

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Sasaki, K., Gotlib, J. R., Mesa, R. A., Newberry, K. J., Ravandi, F., Cortes, J. E., ... Verstovsek, S. (2015). Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis. Leukemia and Lymphoma, 56(7), 2092-2097. https://doi.org/10.3109/10428194.2014.984703

Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis. / Sasaki, Koji; Gotlib, Jason R.; Mesa, Ruben A.; Newberry, Kate J.; Ravandi, Farhad; Cortes, Jorge E.; Kelly, Patrick; Kutok, Jeffery L.; Kantarjian, Hagop M.; Verstovsek, Srdan.

In: Leukemia and Lymphoma, Vol. 56, No. 7, 01.07.2015, p. 2092-2097.

Research output: Contribution to journalArticle

Sasaki, K, Gotlib, JR, Mesa, RA, Newberry, KJ, Ravandi, F, Cortes, JE, Kelly, P, Kutok, JL, Kantarjian, HM & Verstovsek, S 2015, 'Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis', Leukemia and Lymphoma, vol. 56, no. 7, pp. 2092-2097. https://doi.org/10.3109/10428194.2014.984703
Sasaki, Koji ; Gotlib, Jason R. ; Mesa, Ruben A. ; Newberry, Kate J. ; Ravandi, Farhad ; Cortes, Jorge E. ; Kelly, Patrick ; Kutok, Jeffery L. ; Kantarjian, Hagop M. ; Verstovsek, Srdan. / Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis. In: Leukemia and Lymphoma. 2015 ; Vol. 56, No. 7. pp. 2092-2097.
@article{1210a8b6265f44adbe799138b76b817f,
title = "Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis",
abstract = "The clinical safety and efficacy of IPI-926 was evaluated in 14 patients with myelofibrosis in a phase II study. Patients received 160 mg IPI-926 orally in continuous 28-day cycles. The median treatment duration was 5.1 months, and all patients had discontinued treatment by 7.5 months. Nine patients discontinued due to lack of response as determined by the treating physician, two after developing acute leukemia and one due to disease progression/loss of response. Twelve patients had slight reductions in spleen size (less than 50{\%} from baseline), but symptoms did not improve consistently. One patient achieved transfusion independence lasting 5 months. Reductions in GLI1 mRNA and protein levels, JAK2V617F allele burden, degree of fibrosis or cytokine levels were observed in some patients, but were not significant when evaluated for the cohort. Low-grade gastrointestinal/liver abnormalities were the most common toxicities. The results did not support continued evaluation of IPI-926 as a monotherapy in myelofibrosis.",
keywords = "Hedgehog inhibitor, IPI-926, Myelofibrosis, Saridegib",
author = "Koji Sasaki and Gotlib, {Jason R.} and Mesa, {Ruben A.} and Newberry, {Kate J.} and Farhad Ravandi and Cortes, {Jorge E.} and Patrick Kelly and Kutok, {Jeffery L.} and Kantarjian, {Hagop M.} and Srdan Verstovsek",
year = "2015",
month = "7",
day = "1",
doi = "10.3109/10428194.2014.984703",
language = "English (US)",
volume = "56",
pages = "2092--2097",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",
number = "7",

}

TY - JOUR

T1 - Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis

AU - Sasaki, Koji

AU - Gotlib, Jason R.

AU - Mesa, Ruben A.

AU - Newberry, Kate J.

AU - Ravandi, Farhad

AU - Cortes, Jorge E.

AU - Kelly, Patrick

AU - Kutok, Jeffery L.

AU - Kantarjian, Hagop M.

AU - Verstovsek, Srdan

PY - 2015/7/1

Y1 - 2015/7/1

N2 - The clinical safety and efficacy of IPI-926 was evaluated in 14 patients with myelofibrosis in a phase II study. Patients received 160 mg IPI-926 orally in continuous 28-day cycles. The median treatment duration was 5.1 months, and all patients had discontinued treatment by 7.5 months. Nine patients discontinued due to lack of response as determined by the treating physician, two after developing acute leukemia and one due to disease progression/loss of response. Twelve patients had slight reductions in spleen size (less than 50% from baseline), but symptoms did not improve consistently. One patient achieved transfusion independence lasting 5 months. Reductions in GLI1 mRNA and protein levels, JAK2V617F allele burden, degree of fibrosis or cytokine levels were observed in some patients, but were not significant when evaluated for the cohort. Low-grade gastrointestinal/liver abnormalities were the most common toxicities. The results did not support continued evaluation of IPI-926 as a monotherapy in myelofibrosis.

AB - The clinical safety and efficacy of IPI-926 was evaluated in 14 patients with myelofibrosis in a phase II study. Patients received 160 mg IPI-926 orally in continuous 28-day cycles. The median treatment duration was 5.1 months, and all patients had discontinued treatment by 7.5 months. Nine patients discontinued due to lack of response as determined by the treating physician, two after developing acute leukemia and one due to disease progression/loss of response. Twelve patients had slight reductions in spleen size (less than 50% from baseline), but symptoms did not improve consistently. One patient achieved transfusion independence lasting 5 months. Reductions in GLI1 mRNA and protein levels, JAK2V617F allele burden, degree of fibrosis or cytokine levels were observed in some patients, but were not significant when evaluated for the cohort. Low-grade gastrointestinal/liver abnormalities were the most common toxicities. The results did not support continued evaluation of IPI-926 as a monotherapy in myelofibrosis.

KW - Hedgehog inhibitor

KW - IPI-926

KW - Myelofibrosis

KW - Saridegib

UR - http://www.scopus.com/inward/record.url?scp=84938153251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938153251&partnerID=8YFLogxK

U2 - 10.3109/10428194.2014.984703

DO - 10.3109/10428194.2014.984703

M3 - Article

C2 - 25641433

AN - SCOPUS:84938153251

VL - 56

SP - 2092

EP - 2097

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

IS - 7

ER -