Protocol I3X-MC-JHTC

Principal Investigator: JosefPrchal
Keywords: Myelofibrosis , Jak2 Inhibitor Department: Hematology
IRB Number: 00053939 Co Investigator: JosefPrchal
Specialty: Hematology/BMT
Sub Specialties:

Contact Information


Brief Summary

This Phase 1 study is a multicenter, nonrandomized, open-label, dose-escalation study with 2-arms comparing 2 alternative regimens each consisting of a starting dose period of intermittent dosing followed by chronic daily dosing of LY2784544 in patients with myeloproliferative neoplasms.

Inclusion Criteria

1. Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF, either primary myelofibrosis (PMF) or secondary myelofibrosis) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Swerdlow et al. 2008) and meet the additional subtype specific criteria:

A. PV:

   i. has failed or is intolerant of standard therapies or refuses to take standard medications.

B. ET:

   i. has failed or is intolerant of standard therapies or refuses to take standard medications.

C. MF (patients with MF must meet at least one of the following):

   i. has intermediate-1, intermediate-2, or high-risk MF according to the DIPSS plus; or

   ii. has symptomatic MF with spleen greater than 10 cm below left costal margin; or

   iii. has post-polycythemic MF (post-PV MF); or

   iv. has post-essential thrombocythemic MF (post-ET MF)

2. Are ≥18 years of age

3. Have given written informed consent prior to any study-specific procedures

4. 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/mcL, platelets ≥25,000/mcL, platelets ≥50,000 for PV or ET patients.

5.  Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale

6.  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 subject 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.

7.  Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

8.  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.

9.  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.

10.  Are able to swallow capsules/tablets.

11. For subjects 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

12. 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
13. Have a QTc interval >470 msec using Bazett’s formula
14. Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in the study (for example a GI disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome)
15. Are currently being treated with agents that are metabolized by CYP3A4 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)
16. Have received a hematopoietic stem cell transplant
17.  Have a second primary malignancy that in the judgment of the investigator and sponsor, may affect the interpretation of results
18. 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)
19. Have a history of congestive heart failure with New York Heart Association 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