Phase II INCB024360 Study for Patients With Myelodysplastic Syndromes (MDS)

A Phase II Study to Determine the Safety and Efficacy of INCB024360 in Patients With Myelodysplastic Syndromes

The primary purpose of this research study is to assess whether the participant's disease, Myelodysplastic Syndromes (MDS), responds favorably to INCB024360. The study will also evaluate the long-term outcomes of the participant's disease after they have finished taking INCB024360.

Inclusion Criteria:

• Confirmed diagnosis of myelodysplastic syndromes (MDS)

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Adequate organ function:

  • Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN)
  • Aspartic transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN
  • Creatinine ≤ 2 × ULN or Creatinine clearance of > 30 mL/min (using the Cockcroft and Gault Equation)

• Females of childbearing potential must have a negative urine or serum pregnancy test at Screening.

• Women of child-bearing potential and men must agree to use adequate contraception (surgical tubal ligation or vasectomy, double-barrier method of birth control condom with spermicide in conjunction with use of an intrauterine device (IUD) or diaphragm; or sexual abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant, or a male impregnate his female partner, while participating in this study, he/she should inform their treating physician immediately.

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior MDS therapy within 4 weeks of the first dose of study medication. For erythroid stimulating agent and growth factors: prior therapy with epoetin (Procrit) or G-CSF (neupogen) or GM-CSF (leukine) within 2 weeks of the first dose of study medication.

• Has participated in any other trial in which receipt of an investigational study drug occurred within 28 days.

• Has undergone a stem cell, bone marrow or solid organ transplant.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit by the investigator opinion compliance with study requirements

• History of hepatitis or positive serology as follows:

  • Hepatitis B (HepB) screening testing required: HepB SAg (hepatitis B surface antigen); Anti-HepB SAg (antibody against hepatitis B surface antigen); Anti-Hepatitis B core IgG (antibody against hepatitis B core antigen); Anti-Hepatitis B core IgM antibody Note: Subjects with no prior history of hepatitis B infection who have been vaccinated against hepatitis B and who have a positive anti-HepB SAg test as the only evidence of prior exposure may participate in the trial.
  • Hepatitis C screening required: antibody against hepatitis C virus (HCV-antibody); HCV-RNA (serum test for circulating virus, based on detecting RNA)

• Known history human immunodeficiency virus (HIV)

• Is receiving any compound that is known to be a potent inducer or inhibitor of CYP3A4

• Being treated with a monoamine oxidase inhibitor (MAOI), or drug which has significant monoamine oxidase inhibitory activity (meperidine, linezolid, methylene blue) within 3 weeks prior to screening

• Has, by the investigator assessment, an active autoimmune process such as rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc. or is receiving therapy for an autoimmune disease. Subjects with vitiligo, hypothyroidism or eczema may be enrolled after approval by the sponsor.

• Receiving any immunologically based treatment for any reason, including chronic use of systemic steroid at doses ≥ 7.5 mg/day prednisone equivalents; use of inhaled or topical steroids is acceptable.

• Prior malignancies other than MDS for which the subject has not been disease free for ≤ 3 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix.

• Use of any UGT1A9 inhibitor including: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid from screening through follow-up period.

• Have had prior Serotonin Syndrome

• Any unresolved toxicity greater than Grade 2 from previous anticancer therapy, except for stable chronic toxicities not expected to resolve, such as peripheral neurotoxicity