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

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01822691
• Collaborator: Incyte Corporation (Industry)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 19.1
• Patients Per Site Per Month: 0.8

Study Details

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
• 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: Jul 1, 2013
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Feb 1, 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) [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 [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) [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) [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) [Up to 12 months]

   Participants with treatment emergent Other (not including serious) Adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01822691
• Other Study ID Numbers: MCC-17280; I-24360-12-01
• First Posted: Apr 2, 2013
• Last Update Posted: Jan 18, 2016
• Last Verified: Nov 1, 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

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at Moffitt Cancer Center between August 2013 and January 2014.

Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
Period Title: Overall Study
STARTED	15
COMPLETED	13
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 13.3%
>=65 years	13 86.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	72
Sex: Female, Male (Count of Participants)
Female	3 20%
Male	12 80%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	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.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
Measure Participants	15
Stable Disease	12 80%
Complete Response	0 0%
Marrow Complete Response	0 0%
Hematological Improvement	0 0%
Progressive Disease	3 20%

2. Secondary Outcome

Title	Mean Time to Acute Myeloid Leukemia (AML) Progression
Description	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.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
Measure Participants	15
Mean (Full Range) [months]	3.5

3. Secondary Outcome

Title	Median Overall Survival (OS)
Description	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.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
Measure Participants	15
Median (Full Range) [months]	NA

4. Secondary Outcome

Title	Number of Participants With Study Related Serious Adverse Events (SAEs)
Description	Participants with treatment emergent Grade 3 or 4 SAEs according to the NCI Common Terminology Criteria for Adverse Events Version (CTCAE) V4.0.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
Measure Participants	15
Number [participants]	0 0%

5. Secondary Outcome

Title	Number of Participants With Study Treatment Related Adverse Events (AEs)
Description	Participants with treatment emergent Other (not including serious) Adverse events.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
Measure Participants	15
AE of any category	12 80%
Metabolism and Nutrition Disorders	7 46.7%
Gastrointestinal Disorders	6 40%
General Disorders	3 20%
Investigations	3 20%
Immune System Disorders	2 13.3%
Musculoskeletal Disorders	2 13.3%
Skin and Subcutaneous Tissue Disorders	2 13.3%
Infections and Infestations	1 6.7%
Nervous System Disorders	1 6.7%
Psychiatric Disorders	1 6.7%
Respiratory Disorders	1 6.7%

Adverse Events

Time Frame	11 months
Arm/Group Title	INCB024360 Treatment
Arm/Group Description	Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.
All Cause Mortality
	INCB024360 Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	INCB024360 Treatment
	Affected / at Risk (%)	# Events
Total	3/15 (20%)
Immune system disorders
Allergic reaction	1/15 (6.7%)	2
Infections and infestations
Lung infection	1/15 (6.7%)	1
Lymph gland infection	1/15 (6.7%)	1
Vascular disorders
Lymphedema	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	INCB024360 Treatment
	Affected / at Risk (%)	# Events
Total	14/15 (93.3%)
Cardiac disorders
Palpitations	1/15 (6.7%)	1
Endocrine disorders
Adrenal insufficiency	1/15 (6.7%)	1
Hypothyroidism	1/15 (6.7%)	1
Gastrointestinal disorders
Nausea	5/15 (33.3%)	5
Constipation	2/15 (13.3%)	2
Diarrhea	2/15 (13.3%)	2
Vomiting	2/15 (13.3%)	2
Mucositis oral	1/15 (6.7%)	1
Oral hemorrhage	1/15 (6.7%)	1
General disorders
Chills	2/15 (13.3%)	2
Fatigue	2/15 (13.3%)	2
Pain	2/15 (13.3%)	2
Irritability	1/15 (6.7%)	1
Immune system disorders
Immune system disorders - Other, Decreased testosterone	1/15 (6.7%)	1
Immune system disorders - Other, Autoimmune endocrinopathy	1/15 (6.7%)	1
Infections and infestations
Upper respiratory infection	2/15 (13.3%)	2
Bladder infection	1/15 (6.7%)	2
Injury, poisoning and procedural complications
Fall	2/15 (13.3%)	2
Injury, poisoning and procedural complications - Other, Hand wound	1/15 (6.7%)	1
Investigations
Platelet count decreased	4/15 (26.7%)	8
Weight loss	3/15 (20%)	3
Blood prolactin abnormal	1/15 (6.7%)	1
Investigations - Other, Increased chloride	1/15 (6.7%)	1
Neutrophil count decreased	1/15 (6.7%)	1
Metabolism and nutrition disorders
Anorexia	7/15 (46.7%)	7
Hyperglycemia	2/15 (13.3%)	3
Metabolism and nutrition disorders - Other, Decreased chloride	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/15 (6.7%)	1
Bone pain	1/15 (6.7%)	1
Myalgia	1/15 (6.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Bladder cancer	1/15 (6.7%)	1
Nervous system disorders
Dizziness	1/15 (6.7%)	1
Dysgeusia	1/15 (6.7%)	1
Psychiatric disorders
Confusioin	1/15 (6.7%)	1
Depression	1/15 (6.7%)	1
Renal and urinary disorders
Hematuria	1/15 (6.7%)	1
Renal and urinary disorders - Other, Kidney injury	1/15 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Cough	1/15 (6.7%)	1
Dyspnea	1/15 (6.7%)	1
Epistaxis	1/15 (6.7%)	1
Hoarseness	1/15 (6.7%)	1
Sore throat	1/15 (6.7%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	2/15 (13.3%)	2
Alopecia	1/15 (6.7%)	1
Hyperhidrosis	1/15 (6.7%)	1
Skin and subcutaneous tissue disorders - Other, Lip ulcer	1/15 (6.7%)	1
Skin induration	1/15 (6.7%)	1
Skin ulceration	1/15 (6.7%)	1

Limitations/Caveats

The study was closed prior to meeting the overall survival criteria.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.