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

• ClinicalTrials.gov Identifier: NCT01822691
• Recruitment Status: Completed
• First Posted: April 2, 2013
• Results First Posted: January 18, 2016
• Last Update Posted: January 18, 2016
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Incyte Corporation
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Myelodysplastic Syndromes	Drug: INCB024360	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study to Determine the Safety and Efficacy of INCB024360 in Patients With Myelodysplastic Syndromes
• Study Start Date: July 2013
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: February 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: INCB024360 Treatment; 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; 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.; Other Names: inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1); IDO1 inhibitor

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: Up to 12 months ]
   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.

Secondary Outcome Measures :

1. Mean Time to Acute Myeloid Leukemia (AML) Progression [ Time Frame: Up to 12 months ]
   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.
2. Median Overall Survival (OS) [ Time Frame: Up to 24 months ]
   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.
3. Number of Participants With Study Related Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months ]
   Participants with treatment emergent Grade 3 or 4 SAEs according to the NCI Common Terminology Criteria for Adverse Events Version (CTCAE) V4.0.
4. Number of Participants With Study Treatment Related Adverse Events (AEs) [ Time Frame: Up to 12 months ]
   Participants with treatment emergent Other (not including serious) Adverse events.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Incyte Corporation

Investigators

• Principal Investigator: Rami Komrokji, M.D.; H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials website 

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01822691
• Other Study ID Numbers: MCC-17280; I-24360-12-01 ( Other Grant/Funding Number: Incyte )
• First Posted: April 2, 2013
• Results First Posted: January 18, 2016
• Last Update Posted: January 18, 2016
• Last Verified: November 2015

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

myelodysplastic syndromes (MDS); neoplastic stem cell disorders; refractory cytopenias; dysplastic morphological features; acute myeloid leukemia (AML)

Additional relevant MeSH terms:

Preleukemia; Myelodysplastic Syndromes; Syndrome; Disease; Pathologic Processes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Neoplasms