MDACC Study Summary 2010-0167

Study Summary
No. 2010-0167:.......Myeloproliferative Diseases......Srdan Verstovsek......Leukemia

Study Summary Title



Study Summary Number:	2010-0167

Study Title:	A Phase I Study of LY2784544 in Patients with JAK2 V617F-Positive Myeloproliferative Disorders

Physician

New Patient Referral



Name:	Srdan Verstovsek	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-7305 Contact us about clinical trials

General Information



Disease Group:	Myeloproliferative Diseases	Supported By:	Eli Lilly and Company

Phase of Study:	Phase I	Return Visit:

Treatment Agents:	JAK2 Inhibitor LY2784544	Home Care:

Treatment Loc:	Both at MDACC & and Other Sites

Estimated Length of Stay in Houston:


Description/ Intervention:	The goal of this clinical research study is to find the highest tolerable dose of LY2784544 that can be given to patients with myeloproliferative disorders. The safety of this drug will also be studied.

Study Objectives / Outcomes

The primary objective for Part A is to determine the dose and schedule of LY2784544 that may be safely administered to patients with myeloproliferative disorders as supported by pharmacokinetic estimates. For Part B, the primary objective is to confirm the tolerability and safety of the dose and schedule selected in Part A.

The secondary objectives of this study are:
· to characterize the safety and toxicity profile of LY2784544
· to estimate the pharmacokinetic parameters of LY2784544
· to explore potential patient stratification or response biomarkers to LY2784544
· to document any evidence of efficacy by measuring clinical improvement as defined by International Working Group criteria
· to document any improvement in health outcomes or change in frequency of thrombotic and hemorrhagic events after treatment with LY2784544.

Study Status Information



Study Activation / Registration Date:	07/14/2010

IRB Review and Approval Date:	07/14/2010

Study Type:	Phase I

Recruitment Status:	Closed

Projected Accrual:	90

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) 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 and meet the following additional sub-type 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 or high-risk MF according to the Lille scoring system; or ii. has symptomatic MF with spleen greater than 10 cm below left costal margin; or iii. has post-polycythemic MF; or iv. has post-ET MF

2) Have a quantifiable JAK2 V617F mutation.

3) Are equal to or greater than 18 years of age.

4) Have adequate organ function, including: Hepatic: Bilirubin equal to or less than 1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) equal to or less than 2.5 times ULN. Renal: Serum creatinine equal to or less than 1.5 times ULN. Bone Marrow Reserve: Absolute neutrophil count (ANC) equal to or greater than 1000/mcL, platelets equal to or greater than 50,000 /mcL in PV and ET patients or equal to or greater than 25,000/mcL in MF patients.

5) Have discontinued all previous approved therapies for MPDs, 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 (lower or equal to 81mg) acetylsalicylic acid (aspirin) is permitted as well.

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

7) 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.

8) Females with child-bearing potential must have had a negative urine pregnancy test equal to or less than 7 days before the first dose of study drug and must also not be breastfeeding.

9) Are able to swallow capsules.

10) 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.

11) Have given written informed consent prior to any study-specific procedures

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

Exclusion Criteria:

1) 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.

2) 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).

3) 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.

4) Have received a hematopoietic stem cell transplant.

5) Have a second primary malignancy that in the judgment of the Investigator and Sponsor may affect the interpretation of results.

6) Are a candidate for hematopoietic stem cell transplant and transplant is considered to be a treatment of higher priority than participation in this clinical trial. Patients will be considered eligible in the event that a patient has declined transplantation or if in an investigator's opinion a patient is not deemed to be a suitable candidate for hematopoietic stem cell transplant.

7) 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.

8) Have a QTc interval more than 470 msec.

9) 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).

10) 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).

Links

Registration Number: NCT01134120
Study Information on Clinical Trials Registry (clinicaltrials.gov)