Study to assess the best dosage, safety, pharmacokinetic, & pharmacodynamic properties of study drug (TP-3654) in patients with myelofibrosis

Purpose of trial

The standard or usual approved treatments for myelofibrosis are ruxolitinib and fedratinib. TP-3654 is an investigational drug that is being studied by Sumitomo Pharma America, Inc. for the treatment of myelofibrosis. Health Canada has not approved the sale or use of TP-3654 to treat myelofibrosis, although they have allowed its use in this clinical study.TP-3654 has been tested extensively in animals and in the laboratory, as well as in patients with advanced solid tumors. It is not clear if TP-3654 can offer better results than standard treatment. Data has shown that TP-3654 is involved in the inhibition of signaling pathways involved in hematologic cancers. This involves finding ways to stop the communication that are helping these cancer cells grow and spread in the blood or related tissues or disrupting their ability to thrive and multiply. The study medication targets some signals that contribute to the process of slowing down or blocking the abnormal cell growth.

This is a Phase 1/2 study. A Phase I study is a trial of an experimental study drug or treatment which is tested in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Phase I studies are neither expected nor intended to provide a direct personal benefit to participants. A Phase II study is undertaken after preliminary safety testing on a drug or treatment. It is usually conducted on a small number of individuals (100-300 persons), and its goal is to begin to find out what effect it has on your myelofibrosis and to further evaluate its safety.

The purpose of this study is to find the highest dose of a new drug TP-3654 that can be tolerated without causing very severe side effects. This is done by starting at a dose lower than the one that does not cause side effects in animals. Participants are given TP-3654 and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then more potential participants are asked to join this study and are given a higher dose of TP-3654. This will continue until a dose is found that causes tolerable temporary side effects. Doses higher than that will not be given.

The primary purpose of this study is to evaluate the safety of TP-3654 at different doses to find out what effects, if any, it has on people with myelofibrosis. This study will also gain information about the pharmacokinetics (PK) (the process by which a drug is absorbed, distributed, metabolized and eventually eliminated by the body) and pharmacodynamic (PD) biomarkers (which are used to examine the drug effect on the body and/or the tumor) for TP-3654.

Eligibility

Key Inclusion Criteria (From ICF): 
•        Are at least 18 years old at the time of signing the ICF
•        Are able to understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted
•        Are willing and able to adhere to the study visit schedule and other protocol requirements
•        Are willing to avoid pregnancy or fathering children
•        Have been diagnosed with myelofibrosis
•        Were previously treated with a JAK inhibitor (for example, ruxolitinib) and are intolerant, resistant, refractory, or lost response to the treatment, or are ineligible to be treated with medications such as ruxolitinib or fedratinib at the discretion of the investigator

Key Exclusion Criteria (From ICF):
•        Are pregnant or breastfeeding
•        Have a known positive status for HIV or active hepatitis B or C infection