Accelerating drug development in pediatric cancer: A novel Phase i study design of venetoclax in relapsed/refractory malignancies

Andrew E. Place; Kelly Goldsmith; Jean Pierre Bourquin; Mignon L. Loh; Lia Gore; Daniel A. Morgenstern; Yeshwant Sanzgiri; David Hoffman; Ying Zhou; Jeremy A. Ross; Betty Prine; Mohamad Shebley; Megan McNamee; Thalia Farazi; Su Young Kim; Maria Verdugo; Leanne Lash-Fleming; C. Michel Zwaan; Josef Vormoor

doi:10.2217/fon-2018-0121

Accelerating drug development in pediatric cancer: A novel Phase i study design of venetoclax in relapsed/refractory malignancies

Andrew E. Place, Kelly Goldsmith, Jean Pierre Bourquin, Mignon L. Loh, Lia Gore, Daniel A. Morgenstern, Yeshwant Sanzgiri, David Hoffman, Ying Zhou, Jeremy A. Ross, Betty Prine, Mohamad Shebley, Megan McNamee, Thalia Farazi, Su Young Kim, Maria Verdugo, Leanne Lash-Fleming, C. Michel Zwaan, Josef Vormoor

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

Abstract

Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

Original language	English
Pages (from-to)	2115-2129
Number of pages	15
Journal	Future oncology (London, England)
Volume	14
Issue number	21
DOIs	https://doi.org/10.2217/fon-2018-0121
Publication status	Published - Sept 2018
Externally published	Yes

Keywords

ALL
AML
BCL-2
neuroblastoma
NHL
pediatric cancer
relapsed/refractory
venetoclax

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10.2217/fon-2018-0121

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Place, A. E., Goldsmith, K., Bourquin, J. P., Loh, M. L., Gore, L., Morgenstern, D. A., Sanzgiri, Y., Hoffman, D., Zhou, Y., Ross, J. A., Prine, B., Shebley, M., McNamee, M., Farazi, T., Kim, S. Y., Verdugo, M., Lash-Fleming, L., Zwaan, C. M., & Vormoor, J. (2018). Accelerating drug development in pediatric cancer: A novel Phase i study design of venetoclax in relapsed/refractory malignancies. Future oncology (London, England), 14(21), 2115-2129. https://doi.org/10.2217/fon-2018-0121

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title = "Accelerating drug development in pediatric cancer: A novel Phase i study design of venetoclax in relapsed/refractory malignancies",

abstract = "Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).",

keywords = "ALL, AML, BCL-2, neuroblastoma, NHL, pediatric cancer, relapsed/refractory, venetoclax",

author = "Place, {Andrew E.} and Kelly Goldsmith and Bourquin, {Jean Pierre} and Loh, {Mignon L.} and Lia Gore and Morgenstern, {Daniel A.} and Yeshwant Sanzgiri and David Hoffman and Ying Zhou and Ross, {Jeremy A.} and Betty Prine and Mohamad Shebley and Megan McNamee and Thalia Farazi and Kim, {Su Young} and Maria Verdugo and Leanne Lash-Fleming and Zwaan, {C. Michel} and Josef Vormoor",

note = "Publisher Copyright: {\textcopyright} 2018 2018 AbbVie Inc.",

year = "2018",

month = sep,

doi = "10.2217/fon-2018-0121",

language = "English",

volume = "14",

pages = "2115--2129",

journal = "Future oncology (London, England)",

issn = "1744-8301",

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Place, AE, Goldsmith, K, Bourquin, JP, Loh, ML, Gore, L, Morgenstern, DA, Sanzgiri, Y, Hoffman, D, Zhou, Y, Ross, JA, Prine, B, Shebley, M, McNamee, M, Farazi, T, Kim, SY, Verdugo, M, Lash-Fleming, L, Zwaan, CM & Vormoor, J 2018, 'Accelerating drug development in pediatric cancer: A novel Phase i study design of venetoclax in relapsed/refractory malignancies', Future oncology (London, England), vol. 14, no. 21, pp. 2115-2129. https://doi.org/10.2217/fon-2018-0121

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T1 - Accelerating drug development in pediatric cancer

T2 - A novel Phase i study design of venetoclax in relapsed/refractory malignancies

AU - Place, Andrew E.

AU - Goldsmith, Kelly

AU - Bourquin, Jean Pierre

AU - Loh, Mignon L.

AU - Gore, Lia

AU - Morgenstern, Daniel A.

AU - Sanzgiri, Yeshwant

AU - Hoffman, David

AU - Zhou, Ying

AU - Ross, Jeremy A.

AU - Prine, Betty

AU - Shebley, Mohamad

AU - McNamee, Megan

AU - Farazi, Thalia

AU - Kim, Su Young

AU - Verdugo, Maria

AU - Lash-Fleming, Leanne

AU - Zwaan, C. Michel

AU - Vormoor, Josef

PY - 2018/9

Y1 - 2018/9

N2 - Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

AB - Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

KW - ALL

KW - AML

KW - BCL-2

KW - neuroblastoma

KW - NHL

KW - pediatric cancer

KW - relapsed/refractory

KW - venetoclax

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DO - 10.2217/fon-2018-0121

M3 - Article

C2 - 29595064

AN - SCOPUS:85052693575

SN - 1744-8301

VL - 14

SP - 2115

EP - 2129

JO - Future oncology (London, England)

JF - Future oncology (London, England)

IS - 21

ER -

Accelerating drug development in pediatric cancer: A novel Phase i study design of venetoclax in relapsed/refractory malignancies

Abstract

Keywords

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