A Study in Myeloproliferative Disorders

NCT01134120 | Completed Phase 1

• 2 other identifiers: 13201I3X-MC-JHTA
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Myeloproliferative Disorders; Thrombocythemia, Essential; Polycythemia Vera; Primary Myelofibrosis

Outcome Measures

Primary Outcomes (2)

• Determination of a recommended Phase 2 dosing regimen

  Time of first dose until last dose

• Number of participants with clinical significant effects

  Time of first dose until last dose

Secondary Outcomes (3)

• Preliminary pharmacokinetics of LY2784544 (Cmax)

  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

• Preliminary pharmacokinetics of LY2784544 (AUC)

  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

• Malignant clone burden

  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

Study Arms (1)

LY2784544

EXPERIMENTAL

Drug: LY2784544

Interventions

LY2784544 DRUG

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.

LY2784544

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

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, 77030, United States

Location

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, 84132, United States

Location

Related Publications (1)

• 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.

  PMID: 28934680 DERIVED

MeSH Terms

Conditions

Myeloproliferative Disorders; Thrombocythemia, Essential; Polycythemia Vera; Primary Myelofibrosis

Interventions

LY2784544

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Study Officials

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: May 31, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: February 22, 2018
• Last Updated: April 17, 2018

Record last verified: 2018-04

Locations

US (2)