Trial record 1 of 1 for:    NCT01594723
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A Study of LY2784544 in Participants With Myeloproliferative Neoplasms

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01594723
First received: May 1, 2012
Last updated: July 18, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Neoplasms, Hematologic
Drug: 120 mg LY2784544
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of LY2784544 in Patients With Myeloproliferative Neoplasms

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with a Molecular Response (Molecular Response Rate) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Hematological Improvement (Hematological Improvement Rate) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Change in Spleen Size [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Change in Bone Marrow Fibrosis Grade [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Change in Number of Phlebotomies and Transfusions [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Confirmed Response to PD or Death from Any Cause (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Time to Best Response [ Time Frame: Baseline to Confirmed Response (Estimated up to 6 Months) ] [ Designated as safety issue: No ]
  • Change in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Time to Treatment Failure [ Time Frame: Baseline to PD, Death from Any Cause or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Time to Disease Progression [ Time Frame: Baseline to Measured PD (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to PD or Death from Any Cause (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Change in EuroQol - 5 dimensions (EQ-5D) Index Score [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Change in International Prognosis Scoring System Scales (IPSS) [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2784544 [ Time Frame: Predose up to Day 84 ] [ Designated as safety issue: No ]
  • PK: Time of Maximal Concentration (Tmax) of LY2784544 [ Time Frame: Predose up to Day 84 ] [ Designated as safety issue: No ]
  • Change in Liver Size [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Change in 6-item Physician Symptom Assessment [ Time Frame: Baseline until PD or Participant Stops Study (Estimated up to 24 Months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: May 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 120 mg LY2784544
120 milligram (mg) administered orally once daily for 6 cycles (168 days)
Drug: 120 mg LY2784544
Administered orally

  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) 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
  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: NCT01594723

Contacts
Contact: 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

  Show 32 Study Locations
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: NCT01594723     History of Changes
Other Study ID Numbers: 13861, I3X-MC-JHTB
Study First Received: May 1, 2012
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration
Australia: Human Research Ethics Committee
Austria: Ethikkommission
Austria: Federal Office for Safety in Health Care
Canada: Ethics Review Committee
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency

Additional relevant MeSH terms:
Neoplasms
Myeloproliferative Disorders
Hematologic Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Site

ClinicalTrials.gov processed this record on July 22, 2014