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Study Summary
No. 2012-0035:.......Myeloproliferative Diseases......Srdan Verstovsek......Leukemia
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Study Summary Title
Study Summary
Number:
2012-0035
Study Title:An Open-Label, Multiple Simon 2-Stage Study of INCB039110 Administered Orally to
Subjects With Primary Myelofibrosis (PMF), Post Polycythemia Vera-Myelofibrosis (PPVMF)
or Post Essential Thrombocythemia-Myelofibrosis (PET-MF)
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Physician New Patient Referral
Name:Srdan VerstovsekPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7305
Contact us about clinical trials
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General Information
Disease Group:Myeloproliferative DiseasesSupported By:Incyte Corporation
Phase of Study:Phase IIReturn
Visit:
Treatment
Agents:
INCB039110Home Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to study the effects of INCB039110
on spleen size and/or disease symptoms. Researchers want to learn about any
side effects that might occur during or after receiving the drug.
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Study Objectives / Outcomes
Primary Objectives:
· To evaluate preliminary effectiveness of oral INCB039110 in a subject population diagnosed with primary or secondary myelofibrosis (MF) with respect to reduction of symptoms. To evaluate preliminary effectiveness of oral INCB039110 in a subject population diagnosed with primary or secondary MF with respect to reduction of spleen size.
· To evaluate the safety and tolerability of oral INCB039110 in subjects with primary
myelofibrosis (PMF), or myelofibrosis secondary to polycythemia vera or essential
thrombocytopenia (post polycythemia vera-myelofibrosis (PPV-MF) or post essential
thrombocythemia-myelofibrosis (PET-MF)).
Secondary Objectives:
· To evaluate the preliminary effectiveness of oral INCB039110 in a subject population
diagnosed with primary or secondary MF with respect to changes in hemoglobin level and
transfusion dependency.
· To evaluate the preliminary effectiveness of oral INCB039110 in a subject population
diagnosed with primary or secondary MF with respect to changes in total body weight,
Patient Global Impression of Change (PGIC) and European Organization for Research and
Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30).
· To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of oral INCB039110
in subjects with primary or secondary MF.
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Study Status Information
Study Activation / Registration Date:07/23/2012
IRB Review and Approval Date:07/23/2012
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:125
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Subjects who are able to understand and sign an informed consent document (form ICF).

2) Subjects 18 years of age or older.

3) Subjects must be diagnosed with PMF, PPV-MF or PET-MF, according to the Investigator's expert judgment, guided by the criteria outlined in the 2008 World Health Organization criteria for PMF, and the proposed criteria for PPV-MF and PET-MF outlined by the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWGMRT) irrespective of JAK2 mutation status. A bone marrow biopsy will provide the relevant information.(cont. to #4)

4) (cont. from #3) Subjects without circulating blasts at the Screening hematology assessment may use a historical biopsy obtained within the year prior to Screening, provided the report and data are available for the Investigator's review. Subjects who have detectable circulating peripheral blasts at the Screening assessment may use a historical biopsy only if obtained within 2 months prior to Screening, and all data and reports are available for Investigator's review. Subjects without a prior biopsy report as indicated above must have a biopsy at Screening or Baseline or will not be able to enroll in the study.

5) Subjects with MF requiring therapy must have at least 1 point (ie, be Intermediate-1 risk or higher) using the Dynamic International Prognostic Scoring System (DIPSS) prognostic criteria developed by the IWG-MRT(1), using the information from laboratory assessments and ongoing medical history recorded at the Screening visit.

6) Subjects in whom treatment of MF is indicated based on the Investigator's expert judgment.

7) Subjects with active symptoms of MF at the Screening visit as demonstrated by presence of one symptom score of at least 5 or two symptom scores of at least 3 using the Screening Symptom Assessment Form

8) Subjects with a palpable spleen or who have had prior splenectomy.

9) Subjects with hemoglobin values at the Screening visit equal to or greater than 8.0 g/dL and who are willing to receive red blood cell transfusions to treat low hemoglobin levels.

10) Subjects with a platelet count of at least 50 x10^9/L at the Screening visit.

11) Subjects with an absolute neutrophil count (ANC) of at least 1 x10^9/L at the Screening visit.

12) Subjects must have discontinued all drugs used to treat underlying MF disease no later than Day -14 (ie, 7 days before starting the symptom diary). Investigators must determine if withdrawal of current therapy can be accomplished without significant deterioration of the subject's condition in order for such a subject to be eligible for the study.

13) Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

14) Subjects with peripheral blood blast count of < 10% at the Screening and Baseline hematology assessments.

Exclusion Criteria:1) Subjects with a life expectancy of less than 6 months.

2) Subjects in whom MF disease is well controlled with current therapy.

3) Subjects who are categorized as Low risk level by the DIPSS criteria

4) Females who are pregnant or are currently breastfeeding.

5) Subjects of childbearing potential who are unwilling to take appropriate precautions (from Screening through Follow-up) to avoid becoming pregnant or fathering a child. •Females of non-childbearing potential are defined as women who (a) are equal to or greater than 55 years of age with history of amenorrhea for 1 year, OR (b) are surgically sterile for at least 3 months. •For females of childbearing potential, or for males, appropriate precautions are those that are at least 99% effective in preventing the occurrence of pregnancy. These methods should be communicated to the subjects and their understanding confirmed:  Complete abstinence from sexual intercourse  Double barrier methods  condom with spermicide in conjunction with use of an intrauterine device (IUD)  condom with spermicide in conjunction with use of a diaphragm  Oral, injectable, or implanted contraceptives  Tubal ligation or vasectomy (surgical sterilization)

6) Subjects with recent history of inadequate bone marrow reserve as demonstrated by: •Subjects who have received platelet transfusion(s) or who have had ANC levels < 0.5 x109/L in the month prior to Screening.

7) Subjects with inadequate liver or renal function at Screening and Baseline visits as demonstrated by: •Direct bilirubin equal to or greater than 2.0 x the upper limit of laboratory normal (ULN). (NOTE: direct bilirubin will only be determined if total bilirubin is equal to or greater than 2.0 x ULN). •Alanine aminotransferase (ALT) > 2.5x ULN. •Modification of Diet in Renal Disease (MDRD) calculated GFR < 30 mL/min

8) Subjects with clinically meaningful, active bacterial, fungal, parasitic or viral infection which require therapy, or who are HIV positive (Subjects with acute infections requiring treatment should delay Screening/enrollment until the course of therapy has been completed and the event is considered resolved.)

9) Subjects with an invasive malignancy over the previous 2 years except treated basal or squamous carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix and completely resected papillary thyroid and follicular thyroid cancers.

10) Subjects with recent severe or unstable cardiac disease

11) Subjects who have had splenic irradiation within 6 months prior to receiving the first dose of INCB039110.

12) "Subjects being treated concurrently with any prohibited medications, including investigational medication, rifampin, St. John's wort, and potent CYP3A4 inhibitors (excluding ketoconazole.) Refer to protocol section 8.9.2 and appendix 4 for more details."

13) Subjects who have previously received JAK inhibitor therapy for MF may be enrolled only with Sponsor approval.

14) Subjects with active alcohol or drug addiction that would interfere with their ability to comply with the study requirements.

15) Subjects with any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol.

16) Subjects who have unknown transfusion history for at least the 12 weeks prior to Screening. All transfusions in this time period must be recorded in the electronic case report form (eCRF).

17) Subjects who are unable to complete the daily symptom diary, which is available in English, French and Spanish versions.

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Links
Registration Number: NCT01633372
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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