A Study in Myeloproliferative Disorders

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01134120
First received: May 27, 2010
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to find out the safe dose range of the study drug in patients with myeloproliferative disorders.


Condition Intervention Phase
Myeloproliferative Disorders
Thrombocythemia, Essential
Polycythemia Vera
Primary Myelofibrosis
Drug: LY2784544
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of LY2784544 in Patients With JAK2 V617F-Positive Myeloproliferative Disorders

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Determination of a recommended Phase 2 dosing regimen [ Time Frame: Time of first dose until last dose ] [ Designated as safety issue: Yes ]
  • Number of participants with clinical significant effects [ Time Frame: Time of first dose until last dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: April 2010
Estimated Study Completion Date: August 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2784544 Drug: LY2784544
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.

Detailed Description:

The purpose of the study is to learn:

  1. How much and how often LY2784544 should be given to patients
  2. What is the safety profile of LY2784544 and any side effects that might be associated with it
  3. How LY2784544 is taken up, distributed, broken down, and passed out of your body
  4. Whether LY2784544 can help patients with myeloproliferative disorders
  5. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01134120

Locations
United States, Texas
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.
Houston, Texas, United States, 77030
United States, Utah
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.
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01134120     History of Changes
Other Study ID Numbers: 13201, I3X-MC-JHTA
Study First Received: May 27, 2010
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocytosis
Myeloproliferative Disorders
Disease
Thrombocythemia, Essential
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Pathologic Processes
Blood Coagulation Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on September 22, 2014