A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of SAR302503 in Patients with Intermediate-2 or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis with Splenomegaly
You are currently taking part in the 2011-0857 research study. The purpose of this form is to tell you about new information about the study drug that affects your participation in this study.
Disease Group: Myeloproliferative Diseases
Treatment Agent: SAR302503
Treatment Location: Both at MD Anderson & Other Sites
Sponsor: Sanofi US
PRIMARY OBJECTIVE To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of investigational medicinal product (IMP SAR302503) compared to placebo in the reduction of spleen volume as determined by magnetic resonance imaging (MRI) (or computed tomography [CT] scan in patients with contraindications for MRI). SECONDARY OBJECTIVES To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary. To evaluate the OS of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo. To evaluate the Progression Free Survival (PFS) of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo. To evaluate the durability of splenic response. To evaluate the safety of IMP. EXPLORATORY OBJECTIVES To evaluate efficacy, as measured by the rates of CR, PR, CI, SD, progressive disease (PD) and relapse, based on the modified IWG-MRT response criteria. To evaluate the effect of IMP on the JAK2 allele burden. To evaluate the effect of IMP on bone marrow with regard to cytogenetics, cellularity, blast count, and presence or absence of reticulin fibrosis. To evaluate plasma concentrations of IMP. To evaluate the effect on health-related quality of life (QOL) and utility using the EQ-5DTM questionnaire. To evaluate the effect on additional Myeloproliferative Neoplasm (MPN)-associated symptoms, as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).
IRB Review and Approval Date: 07/11/2012
Recruitment Status: Not Accepting
Projected Accrual: 225
1) Diagnosis of PMF or Post-PV MF or Post-ET MF, according to the 2008
World Health Organization and IWG-MRT criteria.
2) Myelofibrosis (MF) classified as high-risk or intermediate-risk level 2, as defined by modified IWG-MRT criteria at screening. For satisfying inclusion criterion #2, patients must have at least 2 risk factors at screening. Risk factors are: Age > 65 years; Hb < 10 g/dL; WBC > 25 x 10(9)/L; Blood blasts >/= 1%; Presence of at least one constitutional symptom at screening (sweats persisting more than one month, weight loss of >10% over a year prior to screening, fever persisting for more than one month).
3) Enlarged spleen, palpable at least 5 cm below costal margin.
4) At least 18 years of age.
5) Eastern Cooperative Oncology Group PS of 0, 1, or 2 at study entry.
6) The following laboratory values within 14 days prior to the initiation of IMP or placebo: ANC >/=1.0 x 10(9)/L; Platelet count >/=50 x 10(9)/L; Serum creatinine </=1.5 x ULN; Serum amylase and lipase </=1.5 x ULN.
7) Life expectancy >/=6 months.
8) Patients with any other prior malignancies are not eligible, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which patient has been disease-free for at least 5 years.
9) Signed informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) form where applicable to participate in the study.
10) Willingness to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures.
1) Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B
and C carriers.
2) AST or ALT >/= 2.5 ULN.
3) Total Bilirubin: exclude if >/=3.0 x ULN; Subjects with total bilirubin between 1.5 - 3.0 x ULN must be excluded if the direct bilirubin fraction is >/= 25% of the total.
4) Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH]).
6) Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), Angrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens, danazol) within 14 days prior to initiation of IMP or placebo; darbepoetin use within 28 days prior to initiation of IMP or placebo. Patients who have had exposure to hydroxyurea (eg, hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to initiation of IMP or placebo.
7) Major surgery within 28 days or radiation within 6 months prior to initiation of IMP or placebo.
8) Prior treatment with a JAK2 inhibitor.
9) Concomitant treatment with or use of pharmaceutical or herbal agents known to be moderate or severe inhibitors or inducers of CYP3A4.
10) Treatment with aspirin in doses >150 mg.
11) Active acute infection requiring antibiotics.
12) Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of IMP or placebo.
13) Participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to initiation of IMP or placebo, unless during a non-treatment phase.
14) Pregnant or lactating female.
15) Women of childbearing potential, unless using effective contraception while on IMP or placebo.
16) Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on IMP or placebo.
17) Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
18) Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or IMP or placebo administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with interpretation of study results and, in the Investigator’s opinion, would render the patient inappropriate for entry into this study.
19) Unable to swallow capsules.
20) Presence of any significant gastric or other disorder that would inhibit absorption of oral medication.
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