This clinical trial is for adult participants who have myelofibrosis for which standard therapy has proven ineffective, or for those who cannot tolerate the standard therapy or are not able to receive the standard therapy.
   
The primary purpose of this study is to evaluate the safety of an experimental compound called TP-3654 at different doses to find out what effects, if any, it has on people. “Experimental” means that the U.S. Food and Drug Administration (FDA) has not yet approved this drug as a prescription medicine and it is only available through research studies like this.

This study will gain information about the process by which the drug is absorbed, distributed, metabolized and eventually eliminated by the body, and examine the drug effect on the body and/or the participant’s tumor.

TP-3654 stops the activity of a protein called PIM1 kinase. Humans with myelofibrosis have more PIM1 kinase protein in their cells than healthy individuals. In mouse experiments, TP-3654 reduced the spleen size and reduced bone marrow fibrosis. TP-3654 has been tested extensively in animals and in the laboratory, as well as in humans with advanced solid tumors.
   
Participants will be instructed to take TP-3654 by mouth once per day or twice per day. Each cycle lasts for 4 weeks and there are no breaks in between cycles.

Participants may remain in the study for as long as they are tolerating and showing benefit from the experimental drug TP-3654.