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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)3883-3888
Number of pages6
JournalAnticancer research
Volume40
Issue number7
DOIs
StatePublished - Jul 1 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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  • Cite this

    Alkhateeb, H. B., Patnaik, M. M., Al-Kali, A., Zblewski, D. L., Wallerich, S., McTavish, H., & Dudek, A. Z. (2020). Phase 1b Study of IGF-Methotrexate Conjugate in the Treatment of High-grade Myelodysplastic Syndromes. Anticancer research, 40(7), 3883-3888. https://doi.org/10.21873/anticanres.14378