Overview

This trial is active, not recruiting.

Condition neoplasms, hematologic
Treatment 120 mg ly2784544
Phase phase 2
Sponsor Eli Lilly and Company
Start date May 2012
End date March 2015
Trial size 110 participants
Trial identifier NCT01594723, 13861, I3X-MC-JHTB

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
120 milligram (mg) administered orally once daily for 6 cycles (168 days)
120 mg ly2784544
Administered orally

Primary Outcomes

Measure
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)

Secondary Outcomes

Measure
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)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase 2 Study of LY2784544 in Patients With Myeloproliferative Neoplasms
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.