A Study of LY2784544 in Participants With Myeloproliferative Neoplasms
Information source: Eli Lilly and Company
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neoplasms, Hematologic
Intervention: 120 mg LY2784544 (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: Eli Lilly and Company Official(s) and/or principal investigator(s): 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), Study Director, Affiliation: Eli Lilly and Company
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.
Clinical Details
Official title: A Phase 2 Study of LY2784544 in Patients With Myeloproliferative Neoplasms
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Percentage of Participants with an Objective Response (Objective Response Rate)
Secondary outcome: Percentage of Participants with a Molecular Response (Molecular Response Rate)Percentage of Participants with Hematological Improvement (Hematological Improvement Rate) Change in Spleen Size Change in Bone Marrow Fibrosis Grade Change in Number of Thrombotic or Hemorrhagic Events Change in Number of Phlebotomies and Transfusions Duration of Response Time to Best Response Change in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Time to Treatment Failure Time to Disease Progression Progression Free Survival (PFS) Change in Activities of Daily Living (ADL)/ Instrumental Activities of Daily Living (IADL) Change in EuroQol - 5 dimensions (EQ-5D) Index Score Change in International Prognosis Scoring System Scales (IPSS) Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2784544 PK: Time of Maximal Concentration (Tmax) of LY2784544 Change in Liver Size Change in 6-item Physician Symptom Assessment
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
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., Wien 1090, Austria
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., Paris 75475, France
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., Jena 07747, Germany
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., Mannheim 68167, Germany
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., Minden 32429, Germany
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., Bologna 40100, Italy
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., Firenze 50100, Italy
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., Barcelona 08036, Spain
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., Madrid 28046, Spain
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., Stockholm SE-118 83, Sweden
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., Uddevalla 45180, Sweden
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., Uppsala 75185, Sweden
Highlands Oncology Group, Fayetteville, Arkansas 72703, United States
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., Garran, Australian Capital Territory 2605, Australia
Providence St. Joseph's Medical Center, Burbank, California 91505, United States
Norwalk Hospital, Norwalk, Connecticut 06850, United States
Lakeland Regional Cancer Center, Lakeland, Florida 33805, United States
Palm Beach Cancer Institue, West Palm Beach, Florida 33401, United States
Ingalls Memorial Hospital, Harvey, Illinois 60426, United States
Indiana Blood & Marrow Transplantation (IBMT), Indianapolis, Indiana 46237, United States
Cancer Center of Kansas, P.A., Wichita, Kansas 67214, United States
University of Maryland- Biological Sciences, Baltimore, Maryland 21201, United States
Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States
Washington University Medical Center, St Louis, Missouri 63110, United States
Nebraska Methodist Hospital, Omaha, Nebraska 68114, United States
Albert Einstein College of Medicine, Bronx, New York 10461, United States
Weill Cornell Medical College, New York, New York 10021, United States
Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States
Mid Ohio Oncology Hematology, Columbus, Ohio 43219, United States
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., Montreal, Quebec H1T 2M4, Canada
The Jones Clinic, Germantown, Tennessee 38138, United States
Sarah Cannon Cancer Center, Nashville, Tennessee 37203, United States
Tennessee Oncology PLLC, Nashville, Tennessee 37203, United States
Joe Arrington Cancer Center, Lubbock, Texas 79410, United States
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., Wodonga, Victoria 3690, Australia
Swedish Medical Center, Seattle, Washington 98104, United States
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., Nedlands, Western Australia 6009, Australia
Dean Medical Center, Madison, Wisconsin 53717, United States
Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States
Additional Information
Starting date: May 2012
Last updated: May 7, 2015
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