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

Study Overview
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Brief Summary
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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.

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

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: INCB024360


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INCB024360 Treatment<br>Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident. | Drug: INCB024360<br>* INCB024360 is an inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO) that is proposed for development for the treatment of malignant diseases. Participants were to receive the study drug in 28 day (4 week) cycles of treatment.<br>* Other names: IDO1 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR, measured by Response Criteria for Patients with Myelodysplastic Syndrome (MDS). According International Working Group (IWG) 2006 criteria (Cheson et al, 2006). Complete Remission (CR), Partial Remission (PR), Marrow CR, and Hematological Improvement (HI)(any cell line). Stable Disease (SD): Failure to achieve at least PR, but no evidence of progression for > 8 weeks. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Time to Acute Myeloid Leukemia (AML) Progression | Disease progression defined as progression to int-2 or high risk International Prognostic Scoring System (IPSS) score or AML, based on World Health Organization (WHO) AML Criteria. | Up to 12 months | 
| Median Overall Survival (OS) | Overall Survival (OS) defined as the time between the start of treatment and death. Treatment Duration is 17 weeks plus optional continuation phase. Study Duration is Treatment Phase followed by survival follow-up. | Up to 24 months | 
| Number of Participants With Study Related Serious Adverse Events (SAEs) | Participants with treatment emergent Grade 3 or 4 SAEs according to the NCI Common Terminology Criteria for Adverse Events Version (CTCAE) V4.0. | Up to 12 months | 
| Number of Participants With Study Treatment Related Adverse Events (AEs) | Participants with treatment emergent Other (not including serious) Adverse events. | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myelodysplastic syndromes (MDS), neoplastic stem cell disorders, refractory cytopenias, dysplastic morphological features, acute myeloid leukemia (AML)