A Study in Myeloproliferative Disorders
Primary Purpose
Myeloproliferative Disorders, Thrombocythemia, Essential, Polycythemia Vera
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LY2784544
Sponsored by
About this trial
This is an interventional treatment trial for Myeloproliferative Disorders
Eligibility Criteria
Inclusion Criteria:
- Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms and meet the following additional sub-type specific criteria:
A. PV: has failed or is intolerant of standard therapies or refuses to take standard medications
B. ET: has failed or is intolerant of standard therapies or refuses to take standard medications
C. MF (patients with MF must meet at least one of the following):
i. has intermediate or high-risk MF according to the Lille scoring system; or
ii. has symptomatic MF with spleen greater than 10 cm below left costal margin; or
iii. has post-polycythemic MF; or
iv. has post-ET MF
- Have a quantifiable JAK2 V617F mutation
- Have discontinued all previous approved therapies for myeloproliferative disorders, including any chemotherapy, immunomodulating therapy (for example, thalidomide, interferon-alpha), immunosuppressive therapy (for example, corticosteroids greater than 10 mg/day prednisone or equivalent), radiotherapy, and erythropoietin, thrombopoietin, or granulocyte colony stimulating factor for at least 14 days and recovered from the acute effects of therapy. Hydroxyurea used to control blood cell counts is permitted at study entry if the subject has been maintained on a stable dose for at least 4 weeks. Low-dose acetylsalicylic acid (aspirin) is permitted as well
Exclusion Criteria:
- Have received treatment within 14 days of the initial dose of study drug with an experimental agent that has not received regulatory approval for any indication
- Are currently being treated with agents that are metabolized by CYP3A4 with a narrow therapeutic margin (for example, alfentanil, cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) or CYP2B6 (for example, cyclophosphamide, ifosfamide, tamoxifen, efavirenz, propofol, methadone, and bupropion)
- Are currently being treated with warfarin or one of its derivatives which is known to alter levels of protein C or protein S. An exception to this criterion will be allowed for patients with a prior history of Budd-Chiari Syndrome who are being treated with warfarin or one of its derivatives
Sites / Locations
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LY2784544
Arm Description
Outcomes
Primary Outcome Measures
Determination of a recommended Phase 2 dosing regimen
Number of participants with clinical significant effects
Secondary Outcome Measures
Preliminary pharmacokinetics of LY2784544 (Cmax)
Preliminary pharmacokinetics of LY2784544 (AUC)
Malignant clone burden
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01134120
Brief Title
A Study in Myeloproliferative Disorders
Official Title
A Phase 1 Study of LY2784544 in Patients With JAK2 V617F-Positive Myeloproliferative Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
February 22, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to find out the safe dose range of the study drug in patients with myeloproliferative disorders.
Detailed Description
The purpose of the study is to learn:
How much and how often LY2784544 should be given to patients
What is the safety profile of LY2784544 and any side effects that might be associated with it
How LY2784544 is taken up, distributed, broken down, and passed out of your body
Whether LY2784544 can help patients with myeloproliferative disorders
If any markers in the blood (biomarkers) can identify patients who will respond better to the study drug.
The planned duration of the study is not fixed. The length of time patients participate in the study will be determined by the investigator/study doctor.
Part A of the study is to determine the dose of the study drug. Part A is divided into two sections, A1 and A2. In Part A1, patients will be given study drug without a lead-in period. In Parts A2 and B, patients will have a lead-in period of 2 or 4 weeks with a low dose of LY2784544 prior to taking a higher dose of LY2784544. Part B of the study is to confirm the safety of the dose and schedule.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloproliferative Disorders, Thrombocythemia, Essential, Polycythemia Vera, Primary Myelofibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
LY2784544
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LY2784544
Intervention Description
LY2784544 will be supplied as a capsule. The study drug will be taken by mouth daily while the patient is on study. In this study, different patients will be treated at different doses of LY2784544 until reaching the highest dose that patients can tolerate.
Primary Outcome Measure Information:
Title
Determination of a recommended Phase 2 dosing regimen
Time Frame
Time of first dose until last dose
Title
Number of participants with clinical significant effects
Time Frame
Time of first dose until last dose
Secondary Outcome Measure Information:
Title
Preliminary pharmacokinetics of LY2784544 (Cmax)
Time Frame
Part A1: Day 1,2,15, and 29; Part A2: Day 7, 14, 21, 28, 29, 56, and 57; Part B: Day 1, 29, 57, and 113
Title
Preliminary pharmacokinetics of LY2784544 (AUC)
Time Frame
Part A1: Day 1,2,15, and 29; Part A2: Day 7, 14, 21, 28, 29, 56, and 57; Part B: Day 1, 29, 57, and 113
Title
Malignant clone burden
Time Frame
Part A1: Baseline (2 times), Weeks 13, 21 and every 6 months while patient is on study; Parts A2 and B: Baseline (2 times), Weeks 5, 8, 17, 25 and every 6 months while patient is on study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms and meet the following additional sub-type specific criteria:
A. PV: has failed or is intolerant of standard therapies or refuses to take standard medications
B. ET: has failed or is intolerant of standard therapies or refuses to take standard medications
C. MF (patients with MF must meet at least one of the following):
i. has intermediate or high-risk MF according to the Lille scoring system; or
ii. has symptomatic MF with spleen greater than 10 cm below left costal margin; or
iii. has post-polycythemic MF; or
iv. has post-ET MF
Have a quantifiable JAK2 V617F mutation
Have discontinued all previous approved therapies for myeloproliferative disorders, including any chemotherapy, immunomodulating therapy (for example, thalidomide, interferon-alpha), immunosuppressive therapy (for example, corticosteroids greater than 10 mg/day prednisone or equivalent), radiotherapy, and erythropoietin, thrombopoietin, or granulocyte colony stimulating factor for at least 14 days and recovered from the acute effects of therapy. Hydroxyurea used to control blood cell counts is permitted at study entry if the subject has been maintained on a stable dose for at least 4 weeks. Low-dose acetylsalicylic acid (aspirin) is permitted as well
Exclusion Criteria:
Have received treatment within 14 days of the initial dose of study drug with an experimental agent that has not received regulatory approval for any indication
Are currently being treated with agents that are metabolized by CYP3A4 with a narrow therapeutic margin (for example, alfentanil, cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) or CYP2B6 (for example, cyclophosphamide, ifosfamide, tamoxifen, efavirenz, propofol, methadone, and bupropion)
Are currently being treated with warfarin or one of its derivatives which is known to alter levels of protein C or protein S. An exception to this criterion will be allowed for patients with a prior history of Budd-Chiari Syndrome who are being treated with warfarin or one of its derivatives
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28934680
Citation
Verstovsek S, Mesa RA, Salama ME, Li L, Pitou C, Nunes FP, Price GL, Giles JL, D'Souza DN, Walgren RA, Prchal JT. A phase 1 study of the Janus kinase 2 (JAK2)V617F inhibitor, gandotinib (LY2784544), in patients with primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Leuk Res. 2017 Oct;61:89-95. doi: 10.1016/j.leukres.2017.08.010. Epub 2017 Aug 31.
Results Reference
derived
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A Study in Myeloproliferative Disorders
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