Neoplasms, Hematologic Clinical Trial
Official title:
A Phase 2 Study of LY2784544 in Patients With Myeloproliferative Neoplasms
| Verified date | March 2024 |
| Source | Eli Lilly and Company |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 110 |
| Est. completion date | December 2024 |
| Est. primary completion date | March 20, 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | 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 |
| Australia | 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 |
| Australia | 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 |
| 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. | Wien | |
| Canada | 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 |
| 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. | Paris | |
| 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. | Jena | |
| 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 | |
| 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 | |
| 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. | Bologna | |
| 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 | |
| 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. | Barcelona | |
| 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 | |
| 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. | Stockholm | |
| 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 | |
| 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 | |
| United States | University of Maryland- Biological Sciences | Baltimore | Maryland |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Albert Einstein College of Medicine | Bronx | New York |
| United States | Providence St. Joseph's Medical Center | Burbank | California |
| United States | Cleveland Clinic Foundation | Cleveland | Ohio |
| United States | Mid Ohio Oncology Hematology | Columbus | Ohio |
| United States | Highlands Oncology Group | Fayetteville | Arkansas |
| United States | The Jones Clinic | Germantown | Tennessee |
| United States | Ingalls Memorial Hospital | Harvey | Illinois |
| United States | Indiana Blood & Marrow Transplantation (IBMT) | Indianapolis | Indiana |
| United States | Lakeland Regional Cancer Center | Lakeland | Florida |
| United States | Joe Arrington Cancer Center | Lubbock | Texas |
| United States | Dean Medical Center | Madison | Wisconsin |
| United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
| United States | Sarah Cannon Cancer Center | Nashville | Tennessee |
| United States | Tennessee Oncology PLLC | Nashville | Tennessee |
| United States | Weill Cornell Medical College | New York | New York |
| United States | Norwalk Hospital | Norwalk | Connecticut |
| United States | Nebraska Methodist Hospital | Omaha | Nebraska |
| United States | Washington University Medical Center | Saint Louis | Missouri |
| United States | Swedish Medical Center | Seattle | Washington |
| United States | Palm Beach Cancer Institue | West Palm Beach | Florida |
| United States | Cancer Center of Kansas, P.A. | Wichita | Kansas |
| Lead Sponsor | Collaborator |
|---|---|
| Eli Lilly and Company |
United States, Australia, Austria, Canada, France, Germany, Italy, Spain, Sweden,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants with an Objective Response (Objective Response Rate) | Baseline until Disease Progression (PD) or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Percentage of Participants with a Molecular Response (Molecular Response Rate) | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Percentage of Participants with Hematological Improvement (Hematological Improvement Rate) | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Change in Spleen Size | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Change in Bone Marrow Fibrosis Grade | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Change in Number of Thrombotic or Hemorrhagic Events | 3 Months prior to Study Drug (historic) until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Change in Number of Phlebotomies and Transfusions | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Duration of Response | Confirmed Response to PD or Death from Any Cause (Estimated up to 24 Months) | ||
| Secondary | Time to Best Response | Baseline to Confirmed Response (Estimated up to 6 Months) | ||
| Secondary | Change in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Time to Treatment Failure | Baseline to PD, Death from Any Cause or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Time to Disease Progression | Baseline to Measured PD (Estimated up to 24 Months) | ||
| Secondary | Progression Free Survival (PFS) | Baseline to PD or Death from Any Cause (Estimated up to 24 Months) | ||
| Secondary | Change in Activities of Daily Living (ADL)/ Instrumental Activities of Daily Living (IADL) | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Change in EuroQol - 5 dimensions (EQ-5D) Index Score | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Change in International Prognosis Scoring System Scales (IPSS) | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2784544 | Predose up to Day 84 | ||
| Secondary | PK: Time of Maximal Concentration (Tmax) of LY2784544 | Predose up to Day 84 | ||
| Secondary | Change in Liver Size | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) | ||
| Secondary | Change in 6-item Physician Symptom Assessment | Baseline until PD or Participant Stops Study (Estimated up to 24 Months) |