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A Study of LY2784544 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: NCT01594723
Recruitment Status : Active, not recruiting
First Posted : May 9, 2012
Last Update Posted : August 25, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE May 1, 2012
First Posted Date  ICMJE May 9, 2012
Last Update Posted Date August 25, 2020
Actual Study Start Date  ICMJE May 22, 2012
Actual Primary Completion Date March 20, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2012)
Percentage of Participants with an Objective Response (Objective Response Rate) [ Time Frame: Baseline until Disease Progression (PD) or Participant Stops Study (Estimated up to 24 Months) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2013)
  • Percentage of Participants with a Molecular Response (Molecular Response Rate) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Percentage of Participants with Hematological Improvement (Hematological Improvement Rate) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Spleen Size [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Bone Marrow Fibrosis Grade [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Number of Thrombotic or Hemorrhagic Events [ Time Frame: 3 Months prior to Study Drug (historic) until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Number of Phlebotomies and Transfusions [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Duration of Response [ Time Frame: Confirmed Response to PD or Death from Any Cause (Estimated up to 24 Months) ]
  • Time to Best Response [ Time Frame: Baseline to Confirmed Response (Estimated up to 6 Months) ]
  • Change in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Time to Treatment Failure [ Time Frame: Baseline to PD, Death from Any Cause or Participant Stops Study (Estimated up to 24 Months) ]
  • Time to Disease Progression [ Time Frame: Baseline to Measured PD (Estimated up to 24 Months) ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to PD or Death from Any Cause (Estimated up to 24 Months) ]
  • Change in Activities of Daily Living (ADL)/ Instrumental Activities of Daily Living (IADL) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in EuroQol - 5 dimensions (EQ-5D) Index Score [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in International Prognosis Scoring System Scales (IPSS) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2784544 [ Time Frame: Predose up to Day 84 ]
  • PK: Time of Maximal Concentration (Tmax) of LY2784544 [ Time Frame: Predose up to Day 84 ]
  • Change in Liver Size [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in 6-item Physician Symptom Assessment [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2012)
  • Percentage of Participants with a Molecular Response (Molecular Response Rate) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Percentage of Participants with Hematological Improvement (Hematological Improvement Rate) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Spleen Size [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Bone Marrow Fibrosis Grade [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Number of Thrombotic or Hemorrhagic Events [ Time Frame: 3 Months prior to Study Drug (historic) until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in Number of Phlebotomies and Transfusions [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Duration of Response [ Time Frame: Confirmed response to PD or death from any cause ]
  • Time to Best Response [ Time Frame: Baseline to Confirmed Response (Estimated up to 6 Months) ]
  • Change in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Time to Treatment Failure [ Time Frame: Baseline to PD, Death from Any Cause or Participant Stops Study (Estimated up to 24 Months) ]
  • Time to Disease Progression [ Time Frame: Baseline to Measured PD (Estimated up to 24 Months) ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to PD or Death from Any Cause (Estimated up to 24 Months) ]
  • Change in Activities of Daily Living (ADL)/ Instrumental Activities of Daily Living (IADL) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in EuroQol - 5 dimensions (EQ-5D) Index Score [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in International Prognosis Scoring System Scales (IPSS) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2784544 [ Time Frame: Predose up to Day 84 ]
  • PK: Time of Maximal Concentration (Tmax) of LY2784544 [ Time Frame: Predose up to Day 84 ]
  • Change in Liver Size [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
  • Change in 6-item Physician Symptom Assessment [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LY2784544 in Participants With Myeloproliferative Neoplasms
Official Title  ICMJE A Phase 2 Study of LY2784544 in Patients With Myeloproliferative Neoplasms
Brief Summary The primary purpose of this study is to measure the response rate in participants with the myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) when treated with LY2784544, including those who have demonstrated an intolerance to, failure of primary response to, or have demonstrated disease progression while on ruxolitinib.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms, Hematologic
Intervention  ICMJE Drug: 120 mg LY2784544
Administered orally
Study Arms  ICMJE Experimental: 120 mg LY2784544
120 milligram (mg) administered orally once daily for 6 cycles (168 days)
Intervention: Drug: 120 mg 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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 25, 2013)
110
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2012)
125
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date March 20, 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) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Swerdlow et al. 2008) and meet the following additional subtype specific criteria:

    • PV: have failed or is intolerant of standard therapies or refuses to take standard medications
    • ET: have failed or is intolerant of standard therapies or refuses to take standard medications
    • MF (participants with MF must meet at least 1 of the following): have intermediate 1, intermediate 2, or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPPS Plus) for Primary Myelofibrosis (Gangat et al. 2011); or have symptomatic MF with spleen greater than 10 centimeter (cm) below left costal margin; or have post-polycythemic MF; or have post-ET MF
  • All PV, ET, and MF participants must meet the following criteria:

    o Have a quantifiable level of janus kinase 2 with a valine to phenylalanine substitution at amino acid 617 (JAK2 V617F) mutation. This inclusion criterion will not apply to the subset of participants in Cohorts 10 and 11 that must be negative for the JAK2 V617F mutation

  • Are ≥ 18 years of age
  • Have given written informed consent prior to any study-specific procedures
  • Have adequate organ function, including: Hepatic: Direct bilirubin ≤1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5 times ULN; Renal: Serum creatinine ≤1.5 times ULN; Bone Marrow Reserve: Absolute neutrophil count (ANC) ≥1000/microliter (mcL), platelets ≥50,000/mcL for participants with ET or PV and ≥25,000/mcL for participants with MF
  • Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have discontinued all previous approved therapies for Myeloproliferative Neoplasms (MPNs), 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 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
  • 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 ≤ 7 days before the first dose of study drug and must also not be breastfeeding
  • Are able to swallow capsules
  • 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
  • Enrollment into Cohort 12 is limited to MF, PV, or ET participants, regardless of mutational status, who, in addition to all other criteria, have demonstrated intolerance to ruxolitinib, failure of primary response to ruxolitinib, or have demonstrated disease progression while on ruxolitinib

Exclusion Criteria:

  • Are currently enrolled in, or discontinued within the last 14 days from a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Have a corrected QT (QTc) interval >470 millisecond (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 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 3A4 enzyme (CYP3A4) with a narrow therapeutic margin (for example, alfentanil, cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) or Cytochrome P450 2B6 enzyme (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 participants with a prior history of Budd-Chiari Syndrome who are being treated with warfarin or one of its derivatives
  • 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 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 >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 Australia,   Austria,   Canada,   France,   Germany,   Italy,   Spain,   Sweden,   United States
Removed Location Countries Netherlands,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01594723
Other Study ID Numbers  ICMJE 13861
I3X-MC-JHTB ( 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 August 15, 2020

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