polycythemia vera, or essential thrombocythemia MedDRA version: 20.1 Level: LLT Classification code 10018864 Term: Haematopoietic neoplasm NOS System Organ Class: 100000004864
Conditions
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Diagnosis of hydroxyurea resistant or intolerant polycythemia vera (PV) or essential thrombocythemia (ET). Polycythemia vera or essential thrombocythemia defined according to the revised WHO criteria Polycythemia vera resistance or intolerance to hydroxyurea is defined as polycythemia vera patients on hydroxyurea with a hematocrit >45%, or phlebotomy twice in the last 6 months and at least once in the last 3 months. Essential thrombocythemia resistance or intolerance to hydroxyurea is defined as essential thrombocythemia patients on hydroxyurea with platelet count >600 x 10 exp9/L. Provide written informed consent to participate. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: Less than 18 years of age. Participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to initiation of study drug, unless during non-treatment phase. (Prior treatment with another JAK2 inhibitor is allowed.) Unwilling to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures. Eastern Cooperative Oncology Group performance status of 3 or 4 at study entry. Splenectomy. Contraindications for undergoing magnetic resonance imaging in patients with palpable spleens (eg, metal implants). Any chemotherapy (eg, hydroxyurea), radiophosphorus therapy, immunomodulatory drug therapy (eg, interferon-alpha), corticosteroids >10 mg/day prednisone or equivalent or anagrelide within 14 days prior to initiation of study drug Active malignancy other than PV or ET, except adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies that have been stable and off therapy for =5 years. Major surgery within 28 days or radiation within 3 months prior to initiation of study drug. Unable to swallow capsules. Active acute infection requiring antibiotics. Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness. Clinically active hepatitis B or C. 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 study drug. Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug 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 make the patient inappropriate for entry into this study. Inadequate organ function Concomitant treatment with or use of drugs or herbal agents known to be at least moderate inhibitors or inducers CYP3A4, unless approved by the Sponsor. Presence of any gastric or other disorder that would inhibit absorption of oral medication. Known hypersensitivity to any excipients in the study drug formulation Pregnant or lactating female. Women of childbearing potential, unless using effective contraception while on study drug. Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of daily oral doses of 100, 200 and 400 mg SAR302503 in patients with polycythemia vera and essential thrombocythemia who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for: Inducing absence of phlebotomy and a hematocrit below 45% for a minimum of 3 months in patients with polycythemia vera, and Reduction of platelet count to =400 x 10 exp9/L for a minimum of 3 months in patients with essential thrombocythemia. ; Secondary Objective: To evaluate the safety of SAR302503. To evaluate the efficacy of daily oral doses of 100, 200 and 400 mg SAR302503 in inducing complete and partial responses (complete response and partial response) per European LeukemiaNet consensus criteria. To evaluate the pharmacokinetics of SAR302503 after single and repeat doses. To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in those patients with JAK2V617F mutation, and STAT3 phosphorylation inhibition. To measure improvement in baseline myeloproliferative neoplasm (MPN)-associated symptoms, as well as overall impact on quality of life, through serial administration of the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). To measure generic health-related quality of life and utility values using the EuroQol Group (EQ-5D™) questionnaire. ; Primary end point(s): Polycythemia vera : Proportion of patients with absence of phlebotomy and hematocrit below 45% for a minimum of 3 months after completion of 8 cycles of therapy Essential thrombocythemia: Proportion of patients with a platelet count = 400 x 10 exp9/L for a minimum of 3 months after completion of 8 cycles of therapy. ;Timepoint(s) of evaluation of this end point: 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 2 years; Secondary end point(s): Characterization of clinicohematologic response defined by European LeukemiaNet sustained for a minimum of 2 months after completion of 8 cycles of therapy. Percent change in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline. Proportion of patients with a 35% reduction in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline Changes in histological, cytogenetic and molecular responses in bone marrow Response (defined as either a 2-point improvement in or resolution of a symptom present at baseline) at the end of Cycles 1, 4, and 8 or end of treatment (EOT), as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). | — |
Countries
France, Italy, Spain, United Kingdom, United States
Contacts
Public ContactMedical Information
sanofi-aventis recherche & développement
Outcome results
None listed