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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

About this trial

This is an interventional treatment trial for Myeloproliferative Disorders

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

NCT ID

NCT01134120

First Posted

May 27, 2010

Last Updated

April 13, 2018

Sponsor

Eli Lilly and Company

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

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

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

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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