A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML

John S. Welch; Haixia Niu; Geoffrey L. Uy; Peter Westervelt; Camille N. Abboud; Ravi Vij; Keith E. Stockerl-Goldstein; Meagan Jacoby; Iskra Pusic; Mark A. Schroeder; John F. Dipersio; Amanda F. Cashen

doi:10.1002/ajh.23735

A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML

John S. Welch, Haixia Niu, Geoffrey L. Uy, Peter Westervelt, Camille N. Abboud, Ravi Vij, Keith E. Stockerl-Goldstein, Meagan Jacoby, Iskra Pusic, Mark A. Schroeder, John F. Dipersio, Amanda F. Cashen

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Abstract

The response rate of non-M3 acute myeloid leukemia (AML) to all trans retinoic acid has been limited. Using Affymetrix expression arrays, we found that in diverse AML blasts RXRA was expressed at higher levels than RARA and that mouse Ctsg-PML-RARA leukemia responded to bexarotene, a ligand for RXRA. We therefore performed a phase I study of combination bexarotene and decitabine in elderly and relapsed AML patients. We found that this combination was well tolerated, although outcomes were modest (1 CRi, and 3 PR among 19 patients). Correlative studies found that patients with clinical response had increased differentiation to bexarotene both in vivo and ex vivo, suggesting that pre-treatment analysis might identify a more susceptible subgroup of patients. Am. J. Hematol. 89:E103-E108, 2014.

Original language	English
Pages (from-to)	E103-E108
Journal	American journal of hematology
Volume	89
Issue number	8
DOIs	https://doi.org/10.1002/ajh.23735
State	Published - Aug 2014

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Welch, J. S., Niu, H., Uy, G. L., Westervelt, P., Abboud, C. N., Vij, R., Stockerl-Goldstein, K. E., Jacoby, M., Pusic, I., Schroeder, M. A., Dipersio, J. F., & Cashen, A. F. (2014). A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML. American journal of hematology, 89(8), E103-E108. https://doi.org/10.1002/ajh.23735

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title = "A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML",

abstract = "The response rate of non-M3 acute myeloid leukemia (AML) to all trans retinoic acid has been limited. Using Affymetrix expression arrays, we found that in diverse AML blasts RXRA was expressed at higher levels than RARA and that mouse Ctsg-PML-RARA leukemia responded to bexarotene, a ligand for RXRA. We therefore performed a phase I study of combination bexarotene and decitabine in elderly and relapsed AML patients. We found that this combination was well tolerated, although outcomes were modest (1 CRi, and 3 PR among 19 patients). Correlative studies found that patients with clinical response had increased differentiation to bexarotene both in vivo and ex vivo, suggesting that pre-treatment analysis might identify a more susceptible subgroup of patients. Am. J. Hematol. 89:E103-E108, 2014.",

author = "Welch, {John S.} and Haixia Niu and Uy, {Geoffrey L.} and Peter Westervelt and Abboud, {Camille N.} and Ravi Vij and Stockerl-Goldstein, {Keith E.} and Meagan Jacoby and Iskra Pusic and Schroeder, {Mark A.} and Dipersio, {John F.} and Cashen, {Amanda F.}",

year = "2014",

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AU - Welch, John S.

AU - Niu, Haixia

AU - Uy, Geoffrey L.

AU - Westervelt, Peter

AU - Abboud, Camille N.

AU - Vij, Ravi

AU - Stockerl-Goldstein, Keith E.

AU - Jacoby, Meagan

AU - Pusic, Iskra

AU - Schroeder, Mark A.

AU - Dipersio, John F.

AU - Cashen, Amanda F.

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AB - The response rate of non-M3 acute myeloid leukemia (AML) to all trans retinoic acid has been limited. Using Affymetrix expression arrays, we found that in diverse AML blasts RXRA was expressed at higher levels than RARA and that mouse Ctsg-PML-RARA leukemia responded to bexarotene, a ligand for RXRA. We therefore performed a phase I study of combination bexarotene and decitabine in elderly and relapsed AML patients. We found that this combination was well tolerated, although outcomes were modest (1 CRi, and 3 PR among 19 patients). Correlative studies found that patients with clinical response had increased differentiation to bexarotene both in vivo and ex vivo, suggesting that pre-treatment analysis might identify a more susceptible subgroup of patients. Am. J. Hematol. 89:E103-E108, 2014.

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JO - American journal of hematology

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ER -

A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML

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