Study of LY2784544 Testing Alternative Dosing in Participants With Myeloproliferative Neoplasms

• ClinicalTrials.gov Identifier: NCT01520220
• Recruitment Status: Completed
• First Posted: January 27, 2012
• Last Update Posted: April 12, 2017
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: January 10, 2012
• First Posted Date: January 27, 2012
• Last Update Posted Date: April 12, 2017
• Actual Study Start Date: June 11, 2012
• Actual Primary Completion Date: June 26, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2013)

• Number of participants with LY2784544 dose limiting toxicities (DLT) [ Time Frame: Baseline through Cycle 1 in Part A (28 day cycles) ]
• Recommended dose range and regimen for Phase 2 studies [ Time Frame: Baseline through Cycle 1 in Part B (28 day cycles) ]

Original Primary Outcome Measures (submitted: January 26, 2012)

• Number of participants with LY2784544 dose limiting toxicities (DLT) [ Time Frame: Baseline through Cycle 2 in Part A (28 day cycles) ]
• Recommended dose range and regimen for Phase 2 studies [ Time Frame: Baseline through Cycle 2 in Part B (28 day cycles) ]

Current Secondary Outcome Measures (submitted: January 14, 2013)

• Pharmacokinetics of LY2784544: Maximum concentration (Cmax) [ Time Frame: Cycle 1 in Part A and Part B (28 day cycles) ]
• Pharmacokinetics of LY2784544: Area under the concentration-time curve (AUC) [ Time Frame: Cycle 1 in Part A and Part B (28 day cycles) ]
• International Working Group (IWG) response [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
• Dynamic International Prognostic Scoring System (DIPSS) Plus [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
• Change in symptom burden as assessed by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Baseline, Last Cycle in Part A and Part B ]
• Change in Myeloproliferative Neoplasm (MPN) Physician Symptom Assessment [ Time Frame: Baseline, Last Cycle in Part A and Part B ]

Original Secondary Outcome Measures (submitted: January 26, 2012)

• Pharmacokinetics of LY2784544: Maximum concentration (Cmax) [ Time Frame: Cycles 1 and 2 in Part A (28 day cycles) ]
• Pharmacokinetics of LY2784544: Area under the concentration-time curve (AUC) [ Time Frame: Cycles 1 and 2 in Part A (28 day cycles) ]
• International Working Group (IWG) response [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
• Dynamic International Prognostic Scoring System (DIPSS) Plus [ Time Frame: Baseline through last Cycle in Part A and Part B (28 day cycles) ]
• Change in symptom burden as assessed by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Baseline, Last Cycle in Part A and Part B ]
• Change in Myeloproliferative Neoplasm (MPN) Physician Symptom Assessment [ Time Frame: Baseline, Last Cycle in Part A and Part B ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: The purpose of this study is to determine a dose of LY2784544 that may be safely administered to participants with myeloproliferative neoplasms.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Myeloproliferative Neoplasms of
• Polycythemia Vera
• Essential Thrombocythemia
• Myelofibrosis

Intervention

Drug: LY2784544

LY2784544 will be taken by mouth per a specified schedule. Each cycle is 28 days.

Study Arms

• Experimental: Part A: LY2784544 Dosing Regimen A
  LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses until reaching the highest dose a participant can tolerate. Each cycle is 28 days.
  Intervention: Drug: LY2784544
• Experimental: Part A: LY2784544 Dosing Regimen B
  LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses until reaching the highest dose a participant can tolerate. Each cycle is 28 days.
  Intervention: Drug: LY2784544
• Experimental: Part B: LY2784544 Dosing Regimen A
  LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses from Part A that are determined to be safe and have potential clinical merit. Each cycle is 28 days.
  Intervention: Drug: LY2784544
• Experimental: Part B: LY2784544 Dosing Regimen B
  LY2784544 will be taken by mouth per a specified schedule. Different participants will be treated at different doses from Part A that are determined to be safe and have potential clinical merit. Each cycle is 28 days.
  Intervention: Drug: LY2784544

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 26, 2012): 100
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 24, 2017
• Actual Primary Completion Date: June 26, 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01520220
• Other Study ID Numbers: 14539; I3X-MC-JHTC ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: 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); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: April 2017