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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01594723




Registration number
NCT01594723
Ethics application status
Date submitted
1/05/2012
Date registered
9/05/2012
Date last updated
25/08/2020

Titles & IDs
Public title
A Study of LY2784544 in Participants With Myeloproliferative Neoplasms
Scientific title
A Phase 2 Study of LY2784544 in Patients With Myeloproliferative Neoplasms
Secondary ID [1] 0 0
I3X-MC-JHTB
Secondary ID [2] 0 0
13861
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Hematologic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 120 mg LY2784544

Experimental: 120 mg LY2784544 - 120 milligram (mg) administered orally once daily for 6 cycles (168 days)


Treatment: Drugs: 120 mg LY2784544
Administered orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with an Objective Response (Objective Response Rate)
Timepoint [1] 0 0
Baseline until Disease Progression (PD) or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [1] 0 0
Percentage of Participants with a Molecular Response (Molecular Response Rate)
Timepoint [1] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [2] 0 0
Percentage of Participants with Hematological Improvement (Hematological Improvement Rate)
Timepoint [2] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [3] 0 0
Change in Spleen Size
Timepoint [3] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [4] 0 0
Change in Bone Marrow Fibrosis Grade
Timepoint [4] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [5] 0 0
Change in Number of Thrombotic or Hemorrhagic Events
Timepoint [5] 0 0
3 Months prior to Study Drug (historic) until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [6] 0 0
Change in Number of Phlebotomies and Transfusions
Timepoint [6] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [7] 0 0
Duration of Response
Timepoint [7] 0 0
Confirmed Response to PD or Death from Any Cause (Estimated up to 24 Months)
Secondary outcome [8] 0 0
Time to Best Response
Timepoint [8] 0 0
Baseline to Confirmed Response (Estimated up to 6 Months)
Secondary outcome [9] 0 0
Change in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Timepoint [9] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [10] 0 0
Time to Treatment Failure
Timepoint [10] 0 0
Baseline to PD, Death from Any Cause or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [11] 0 0
Time to Disease Progression
Timepoint [11] 0 0
Baseline to Measured PD (Estimated up to 24 Months)
Secondary outcome [12] 0 0
Progression Free Survival (PFS)
Timepoint [12] 0 0
Baseline to PD or Death from Any Cause (Estimated up to 24 Months)
Secondary outcome [13] 0 0
Change in Activities of Daily Living (ADL)/ Instrumental Activities of Daily Living (IADL)
Timepoint [13] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [14] 0 0
Change in EuroQol - 5 dimensions (EQ-5D) Index Score
Timepoint [14] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [15] 0 0
Change in International Prognosis Scoring System Scales (IPSS)
Timepoint [15] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [16] 0 0
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2784544
Timepoint [16] 0 0
Predose up to Day 84
Secondary outcome [17] 0 0
PK: Time of Maximal Concentration (Tmax) of LY2784544
Timepoint [17] 0 0
Predose up to Day 84
Secondary outcome [18] 0 0
Change in Liver Size
Timepoint [18] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)
Secondary outcome [19] 0 0
Change in 6-item Physician Symptom Assessment
Timepoint [19] 0 0
Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,VIC,WA
Recruitment hospital [1] 0 0
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
Recruitment hospital [2] 0 0
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
Recruitment hospital [3] 0 0
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
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
3690 - Wodonga
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
Austria
State/province [18] 0 0
Wien
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
Germany
State/province [21] 0 0
Jena
Country [22] 0 0
Germany
State/province [22] 0 0
Mannheim
Country [23] 0 0
Germany
State/province [23] 0 0
Minden
Country [24] 0 0
Italy
State/province [24] 0 0
Bologna
Country [25] 0 0
Italy
State/province [25] 0 0
Firenze
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Sweden
State/province [28] 0 0
Stockholm
Country [29] 0 0
Sweden
State/province [29] 0 0
Uddevalla
Country [30] 0 0
Sweden
State/province [30] 0 0
Uppsala

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT01594723
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications