Study of LY2784544 Testing Alternative Dosing in Participants With Myeloproliferative Neoplasms

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01520220
First received: January 10, 2012
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to determine a dose of LY2784544 that may be safely administered to participants with myeloproliferative neoplasms.


Condition Intervention Phase
Myeloproliferative Neoplasms of
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
Drug: LY2784544
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of LY2784544 Testing Alternative Dosing Regimens in Patients With Myeloproliferative Neoplasms

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of participants with LY2784544 dose limiting toxicities (DLT) [ Time Frame: Baseline through Cycle 1 in Part A (28 day cycles) ] [ Designated as safety issue: Yes ]
  • Recommended dose range and regimen for Phase 2 studies [ Time Frame: Baseline through Cycle 1 in Part B (28 day cycles) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics of LY2784544: Maximum concentration (Cmax) [ Time Frame: Cycle 1 in Part A and Part B (28 day cycles) ] [ Designated as safety issue: No ]
  • Pharmacokinetics of LY2784544: Area under the concentration-time curve (AUC) [ Time Frame: Cycle 1 in Part A and Part B (28 day cycles) ] [ Designated as safety issue: No ]
  • International Working Group (IWG) response [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ] [ Designated as safety issue: No ]
  • Dynamic International Prognostic Scoring System (DIPSS) Plus [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ] [ Designated as safety issue: No ]
  • Change in symptom burden as assessed by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Baseline, Last Cycle in Part A and Part B ] [ Designated as safety issue: No ]
  • Change in Myeloproliferative Neoplasm (MPN) Physician Symptom Assessment [ Time Frame: Baseline, Last Cycle in Part A and Part B ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: June 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: LY2784544 Dosing Regimen A
LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses until reaching the highest dose a participant can tolerate. Each cycle is 28 days.
Drug: LY2784544
LY2784544 will be taken by mouth per a specified schedule. Each cycle is 28 days.
Experimental: Part A: LY2784544 Dosing Regimen B
LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses until reaching the highest dose a participant can tolerate. Each cycle is 28 days.
Drug: LY2784544
LY2784544 will be taken by mouth per a specified schedule. Each cycle is 28 days.
Experimental: Part B: LY2784544 Dosing Regimen A
LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses from Part A that are determined to be safe and have potential clinical merit. Each cycle is 28 days.
Drug: LY2784544
LY2784544 will be taken by mouth per a specified schedule. Each cycle is 28 days.
Experimental: Part B: LY2784544 Dosing Regimen B
LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses from Part A that are determined to be safe and have potential clinical merit. Each cycle is 28 days.
Drug: LY2784544
LY2784544 will be taken by mouth per a specified schedule. Each cycle is 28 days.

  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, primary or secondary) PV and ET participants must have failed or are intolerant of standard therapies or refuse to take standard medications

MF participants must meet at least one of the following criteria:

  • Have intermediate-1, intermediate-2, or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPSS) plus; or
  • Have symptomatic MF with spleen greater than 10 cm below left costal margin; or
  • Have post-polycythemic MF (post-PV MF); or
  • Have post-essential thrombocythemic MF (post-ET MF)

All participants must meet the following criteria:

  • Have given written informed consent prior to any study-specific procedures
  • Have adequate organ function, including:
  • Hepatic: Direct bilirubin less than or equal to 1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) less than or equal to 2.5 times ULN
  • Renal: Serum creatinine less than or equal to 1.5 times ULN
  • Bone Marrow Reserve: Absolute neutrophil count (ANC) ≥1000/mcL, platelets ≥25,000/mcL, platelets ≥50,000 for PV or ET participants.
  • Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have discontinued all previous approved therapies for MF, including any chemotherapy, immunomodulating therapy (for example, thalidomide, interferon-alpha), immunosuppressive therapy (for example, corticosteroids >10 mg/day prednisone or equivalent), radiotherapy, and erythropoietin, thrombopoietin, or granulocyte colony-stimulating factor (GSF) 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 participant has been maintained on a stable dose for at least 4 weeks. Low dose acetylsalicylic acid (aspirin; 81 or 100 mg) is permitted as well
  • Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
  • Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug
  • Females with child-bearing potential must have had a negative urine pregnancy test less than or equal to 7 days before the first dose of study drug and must also not be breastfeeding
  • Are able to swallow capsules/tablets
  • For participants who have undergone recent major surgery, at least 28 days must have elapsed between surgery and study participation, and the participant must have achieved, in the opinion of the treating physician, at least a good recovery from the surgical procedure

Exclusion Criteria:

Potential participants may not be included in the study if any of the following apply during screening:

  • 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
  • Have a QTc interval >470 milliseconds (msec) using Bazett's formula
  • Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in the study (for example, a gastrointestinal (GI) disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome)
  • Are currently being treated with agents that are metabolized by cytochrome P450 (CYP)3A4 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)
  • Have received a hematopoietic stem cell transplant
  • Have a second primary malignancy that in the judgment of the investigator and sponsor, may affect the interpretation of the results
  • Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required)
  • Have a history of congestive heart failure with New York Heart Association (NYHA) Class greater than 2 (NYHA Class 1 and 2 are eligible), unstable angina, recent myocardial infarction (within 6 months prior to administration of study drug), or documented history of ventricular arrhythmia
  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: NCT01520220

Locations
United States, Alabama
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.
Birmingham, Alabama, United States, 35249
United States, Arizona
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.
Scottsdale, Arizona, United States, 85259
United States, Arkansas
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.
Fayetteville, Arkansas, United States, 72703
United States, District of Columbia
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.
Washington, District of Columbia, United States, 20007
United States, Florida
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.
Jacksonville, Florida, United States, 32224
United States, Hawaii
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.
Honolulu, Hawaii, United States, 96813
United States, South Carolina
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.
Charleston, South Carolina, United States, 29425
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
United States, Wisconsin
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.
Milwaukee, Wisconsin, United States, 53226
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: NCT01520220     History of Changes
Other Study ID Numbers: 14539, I3X-MC-JHTC
Study First Received: January 10, 2012
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 23, 2014