1. Phase 1b Study of IGF-Methotrexate Conjugate in the Treatment of High-grade Myelodysplastic Syndromes
- Author
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Aref Al-Kali, Hassan B. Alkhateeb, Arkadiusz Z. Dudek, Samantha Wallerich, Darci Zblewski, Hugh McTavish, and Mrinal M. Patnaik
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Immunoconjugates ,Phases of clinical research ,Chronic myelomonocytic leukemia ,Gastroenterology ,Receptor, IGF Type 1 ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Molecular Targeted Therapy ,Insulin-Like Growth Factor I ,Aged ,IGF-methotrexate Conjugate ,Aged, 80 and over ,Cytopenia ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Methotrexate ,Oncology ,Myelodysplastic Syndromes ,Bone marrow ,Neoplasm Grading ,business ,medicine.drug - 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.
- Published
- 2020