Phase 1b study of IGF-methotrexate conjugate in the treatment of high-grade myelodysplastic syndromes

Hassan B. Alkhateeb; Mrinal M. Patnaik; Aref Al-Kali; Darci L. Zblewski; Samantha Wallerich; Hugh McTavish; Arkadiusz Z. Dudek

doi:10.21873/ANTICANRES.14378

Phase 1b study of IGF-methotrexate conjugate in the treatment of high-grade myelodysplastic syndromes

Hassan B. Alkhateeb, Mrinal M. Patnaik, Aref Al-Kali, Darci L. Zblewski, Samantha Wallerich, Hugh McTavish, Arkadiusz Z. Dudek

Hematology

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

Abstract

Background/Aim: The insulin-like growth factor type 1 receptor (IGF-1R) is overexpressed in myelodysplastic syndrome (MDS) cells, and 765IGF-Methotrexate (IGF-MTX) is a conjugate of methotrexate and a variant of insulin-like growth factor-1 (IGF-1) designed to selectively target cancer cells through binding to IGF-1R. The aim of this study was to determine whether IGF-MTX would be effective to treat MDS. Patients and Methods: In this phase I clinical trial, two patients with high grade MDS or oligoblastic acute myeloid leukemia (O-AML) that had failed standard therapy were treated with IGF-MTX. Results: No dose-limiting toxicity was observed. Both patients had stable or improved cell counts and CD34+ myelodysplastic cell counts and exceeded their life expectancy (both alive at 1.9 years despite a life expectancy of less than 6 months). Bone marrow blast counts decreased from 22% to 5% in one patient, and from 17% to 16% in the other. Conclusion: In conclusion, IGF-MTX at 0.20 μM equivalents per kg was well tolerated, caused no cytopenia, and produced stable disease and extension of life.

Original language	English (US)
Pages (from-to)	3883-3888
Number of pages	6
Journal	Anticancer research
Volume	40
Issue number	7
DOIs	https://doi.org/10.21873/ANTICANRES.14378
State	Published - Jul 2020

Keywords

Chronic myelomonocytic leukemia
IGF-1R
IGF-MTX
Myelodysplastic syndrome
Oligoblastic acute myeloid leukemia
Phase 1 study

ASJC Scopus subject areas

Oncology
Cancer Research

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10.21873/ANTICANRES.14378

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title = "Phase 1b study of IGF-methotrexate conjugate in the treatment of high-grade myelodysplastic syndromes",

abstract = "Background/Aim: The insulin-like growth factor type 1 receptor (IGF-1R) is overexpressed in myelodysplastic syndrome (MDS) cells, and 765IGF-Methotrexate (IGF-MTX) is a conjugate of methotrexate and a variant of insulin-like growth factor-1 (IGF-1) designed to selectively target cancer cells through binding to IGF-1R. The aim of this study was to determine whether IGF-MTX would be effective to treat MDS. Patients and Methods: In this phase I clinical trial, two patients with high grade MDS or oligoblastic acute myeloid leukemia (O-AML) that had failed standard therapy were treated with IGF-MTX. Results: No dose-limiting toxicity was observed. Both patients had stable or improved cell counts and CD34+ myelodysplastic cell counts and exceeded their life expectancy (both alive at 1.9 years despite a life expectancy of less than 6 months). Bone marrow blast counts decreased from 22% to 5% in one patient, and from 17% to 16% in the other. Conclusion: In conclusion, IGF-MTX at 0.20 μM equivalents per kg was well tolerated, caused no cytopenia, and produced stable disease and extension of life.",

keywords = "Chronic myelomonocytic leukemia, IGF-1R, IGF-MTX, Myelodysplastic syndrome, Oligoblastic acute myeloid leukemia, Phase 1 study",

author = "Alkhateeb, {Hassan B.} and Patnaik, {Mrinal M.} and Aref Al-Kali and Zblewski, {Darci L.} and Samantha Wallerich and Hugh McTavish and Dudek, {Arkadiusz Z.}",

year = "2020",

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doi = "10.21873/ANTICANRES.14378",

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pages = "3883--3888",

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T1 - Phase 1b study of IGF-methotrexate conjugate in the treatment of high-grade myelodysplastic syndromes

AU - Alkhateeb, Hassan B.

AU - Patnaik, Mrinal M.

AU - Al-Kali, Aref

AU - Zblewski, Darci L.

AU - Wallerich, Samantha

AU - McTavish, Hugh

AU - Dudek, Arkadiusz Z.

PY - 2020/7

Y1 - 2020/7

N2 - Background/Aim: The insulin-like growth factor type 1 receptor (IGF-1R) is overexpressed in myelodysplastic syndrome (MDS) cells, and 765IGF-Methotrexate (IGF-MTX) is a conjugate of methotrexate and a variant of insulin-like growth factor-1 (IGF-1) designed to selectively target cancer cells through binding to IGF-1R. The aim of this study was to determine whether IGF-MTX would be effective to treat MDS. Patients and Methods: In this phase I clinical trial, two patients with high grade MDS or oligoblastic acute myeloid leukemia (O-AML) that had failed standard therapy were treated with IGF-MTX. Results: No dose-limiting toxicity was observed. Both patients had stable or improved cell counts and CD34+ myelodysplastic cell counts and exceeded their life expectancy (both alive at 1.9 years despite a life expectancy of less than 6 months). Bone marrow blast counts decreased from 22% to 5% in one patient, and from 17% to 16% in the other. Conclusion: In conclusion, IGF-MTX at 0.20 μM equivalents per kg was well tolerated, caused no cytopenia, and produced stable disease and extension of life.

AB - Background/Aim: The insulin-like growth factor type 1 receptor (IGF-1R) is overexpressed in myelodysplastic syndrome (MDS) cells, and 765IGF-Methotrexate (IGF-MTX) is a conjugate of methotrexate and a variant of insulin-like growth factor-1 (IGF-1) designed to selectively target cancer cells through binding to IGF-1R. The aim of this study was to determine whether IGF-MTX would be effective to treat MDS. Patients and Methods: In this phase I clinical trial, two patients with high grade MDS or oligoblastic acute myeloid leukemia (O-AML) that had failed standard therapy were treated with IGF-MTX. Results: No dose-limiting toxicity was observed. Both patients had stable or improved cell counts and CD34+ myelodysplastic cell counts and exceeded their life expectancy (both alive at 1.9 years despite a life expectancy of less than 6 months). Bone marrow blast counts decreased from 22% to 5% in one patient, and from 17% to 16% in the other. Conclusion: In conclusion, IGF-MTX at 0.20 μM equivalents per kg was well tolerated, caused no cytopenia, and produced stable disease and extension of life.

KW - Chronic myelomonocytic leukemia

KW - IGF-1R

KW - IGF-MTX

KW - Myelodysplastic syndrome

KW - Oligoblastic acute myeloid leukemia

KW - Phase 1 study

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Phase 1b study of IGF-methotrexate conjugate in the treatment of high-grade myelodysplastic syndromes

Abstract

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