A Study of LY2784544 in Participants With Myeloproliferative Neoplasms

Status: Recruiting
Phase:
Diagnosis: Leukemia/MDS
NCT ID: NCT01594723 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 12-174

 

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.

 

Conducting Institutions:
Brigham and Women's Hospital, Dana-Farber Cancer Institute

Overall PI:
Martha Wadleigh, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Contacts:
Dana-Farber Cancer Institute: Ilene Galinsky, 617-632-3902, igalinsky@partners.org

Eligibility 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 (patients 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 cm below left costal margin; or have post-polycythemic MF; or have post-ET MF. - All PV, ET, and MF patients must meet the following criteria: - Have a quantifiable level of janus kinase 2 with a valine to phenylalanine substitution at amino acid 617 (JAK2 V617F) mutation. For patients in Dose Level 3, this inclusion criterion will not apply to the subset of patients in Cohorts 10 and 11 that are required to be negative for the JAK2 V617F mutation. This subset of patients must be negative for the mutation with unquantifiable levels of JAK2 V617F - Are ≥ 18 years of age - Have given written informed consent prior to any study-specific procedures - Have adequate organ function, including: Hepatic: 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 patients with ET or PV and ≥ 25,000/mcL for patients 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 patients who have undergone recent major surgery, at least 28 days must have elapsed between surgery and study participation and the subject must have achieved, in the opinion of the treating physician, at least a good recovery from the surgical procedure 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 patients 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
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