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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

Page last updated: August 23, 2015

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