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Study of LY2784544 Testing Alternative Dosing in Participants With Myeloproliferative Neoplasms

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01520220
Recruitment Status : Completed
First Posted : January 27, 2012
Last Update Posted : April 12, 2017
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE January 10, 2012
First Posted Date  ICMJE January 27, 2012
Last Update Posted Date April 12, 2017
Actual Study Start Date  ICMJE June 11, 2012
Actual Primary Completion Date June 26, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2013)
  • Number of participants with LY2784544 dose limiting toxicities (DLT) [ Time Frame: Baseline through Cycle 1 in Part A (28 day cycles) ]
  • Recommended dose range and regimen for Phase 2 studies [ Time Frame: Baseline through Cycle 1 in Part B (28 day cycles) ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
  • Number of participants with LY2784544 dose limiting toxicities (DLT) [ Time Frame: Baseline through Cycle 2 in Part A (28 day cycles) ]
  • Recommended dose range and regimen for Phase 2 studies [ Time Frame: Baseline through Cycle 2 in Part B (28 day cycles) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2013)
  • Pharmacokinetics of LY2784544: Maximum concentration (Cmax) [ Time Frame: Cycle 1 in Part A and Part B (28 day cycles) ]
  • Pharmacokinetics of LY2784544: Area under the concentration-time curve (AUC) [ Time Frame: Cycle 1 in Part A and Part B (28 day cycles) ]
  • International Working Group (IWG) response [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
  • Dynamic International Prognostic Scoring System (DIPSS) Plus [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
  • 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 ]
  • Change in Myeloproliferative Neoplasm (MPN) Physician Symptom Assessment [ Time Frame: Baseline, Last Cycle in Part A and Part B ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
  • Pharmacokinetics of LY2784544: Maximum concentration (Cmax) [ Time Frame: Cycles 1 and 2 in Part A (28 day cycles) ]
  • Pharmacokinetics of LY2784544: Area under the concentration-time curve (AUC) [ Time Frame: Cycles 1 and 2 in Part A (28 day cycles) ]
  • International Working Group (IWG) response [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
  • Dynamic International Prognostic Scoring System (DIPSS) Plus [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
  • 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 ]
  • Change in Myeloproliferative Neoplasm (MPN) Physician Symptom Assessment [ Time Frame: Baseline, Last Cycle in Part A and Part B ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of LY2784544 Testing Alternative Dosing in Participants With Myeloproliferative Neoplasms
Official Title  ICMJE A Phase 1 Study of LY2784544 Testing Alternative Dosing Regimens in Patients With Myeloproliferative Neoplasms
Brief Summary The purpose of this study is to determine a dose of LY2784544 that may be safely administered to participants with myeloproliferative neoplasms.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myeloproliferative Neoplasms of
  • Polycythemia Vera
  • Essential Thrombocythemia
  • Myelofibrosis
Intervention  ICMJE Drug: LY2784544
LY2784544 will be taken by mouth per a specified schedule. Each cycle is 28 days.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: LY2784544
  • 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.
    Intervention: Drug: LY2784544
  • 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.
    Intervention: Drug: LY2784544
  • 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.
    Intervention: Drug: LY2784544
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 26, 2012)
100
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 24, 2017
Actual Primary Completion Date June 26, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01520220
Other Study ID Numbers  ICMJE 14539
I3X-MC-JHTC ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP