Clinical trial NCT01520220: Study of LY2784544 Testing Alternative Dosing in Participants With Myeloproliferative Neoplasms
Official title: A Phase 1 Study of LY2784544 Testing Alternative Dosing Regimens in Patients With Myeloproliferative Neoplasms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myeloproliferative Neoplasms of
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-01-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine a dose of LY2784544 that may be safely administered to participants with myeloproliferative neoplasms.


Eligibility criteria: Inclusion Criteria:

Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF, primary or secondary) PV and ET participants must have failed or are intolerant of standard therapies or refuse to take standard medications

MF participants must meet at least one of the following criteria:

* Have intermediate-1, intermediate-2, or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPSS) plus; or
* Have symptomatic MF with spleen greater than 10 cm below left costal margin; or
* Have post-polycythemic MF (post-PV MF); or
* Have post-essential thrombocythemic MF (post-ET MF)

All participants must meet the following criteria:

* Have given written informed consent prior to any study-specific procedures
* Have adequate organ function, including:
* Hepatic: Direct bilirubin less than or equal to 1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) less than or equal to 2.5 times ULN
* Renal: Serum creatinine less than or equal to 1.5 times ULN
* Bone Marrow Reserve: Absolute neutrophil count (ANC) ≥1000/mcL, platelets ≥25,000/mcL, platelets ≥50,000 for PV or ET participants.
* Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale
* Have discontinued all previous approved therapies for MF, 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 (GSF) 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 participant has been maintained on a stable dose for at least 4 weeks. Low dose acetylsalicylic acid (aspirin; 81 or 100 mg) 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 less than or equal to 7 days before the first dose of study drug and must also not be breastfeeding
* Are able to swallow capsules/tablets
* 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

Exclusion Criteria:

Potential participants may not be included in the study if any of the following apply during screening:

* Have received treatment within 14 days of the initial dose of study drug with an experimental agent that has not received regulatory approval for any indication
* Have a QTc interval \>470 milliseconds (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 (GI) 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 (CYP)3A4 with a narrow therapeutic margin (for example, alfentanil, cyclosporine,diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) or CYP2B6 (for example, cyclophosphamide, ifosfamide, tamoxifen, efavirenz, propofol, methadone, and bupropion)
* 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 the 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 greater than 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

Primary outcomes:
measure: Number of participants with LY2784544 dose limiting toxicities (DLT)
timeFrame: Baseline through Cycle 1 in Part A (28 day cycles)
measure: Recommended dose range and regimen for Phase 2 studies
timeFrame: Baseline through Cycle 1 in Part B (28 day cycles)
Secondary outcomes:
measure: Pharmacokinetics of LY2784544: Maximum concentration (Cmax)
timeFrame: Cycle 1 in Part A and Part B (28 day cycles)
measure: Pharmacokinetics of LY2784544: Area under the concentration-time curve (AUC)
timeFrame: Cycle 1 in Part A and Part B (28 day cycles)
measure: International Working Group (IWG) response
timeFrame: Baseline through last Cycle in Part A and Part B (28 day cycles)
measure: Dynamic International Prognostic Scoring System (DIPSS) Plus
timeFrame: Baseline through last Cycle in Part A and Part B (28 day cycles)
measure: Change in symptom burden as assessed by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
timeFrame: Baseline, Last Cycle in Part A and Part B
measure: Change in Myeloproliferative Neoplasm (MPN) Physician Symptom Assessment
timeFrame: Baseline, Last Cycle in Part A and Part B
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 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.
state: Alabama
city: Scottsdale
country: United States
facility: 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.
state: Arizona
city: Fayetteville
country: United States
facility: 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.
state: Arkansas
city: Washington
country: United States
facility: 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.
state: District of Columbia
city: Jacksonville
country: United States
facility: 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.
state: Florida
city: Honolulu
country: United States
facility: 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.
state: Hawaii
city: Charleston
country: United States
facility: 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.
state: South Carolina
city: Salt Lake City
country: United States
facility: 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.
state: Utah
city: Milwaukee
country: United States
facility: 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.
state: Wisconsin
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: