Hematopoietic Neoplasm
Conditions
Brief summary
Primary Objective: \- To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of intermediate-1 with symptoms, Intermediate-2 or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocythemia myelofibrosis (Post-ET MF) based on the reduction of spleen volume at the end of 6 treatment cycles; Secondary Objectives: * To evaluate the effect of SAR302503 on Myelofibrosis (MF) associated symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary * To evaluate the durability of splenic response * To evaluate the splenic response to SAR302503 by palpation at the end of Cycle 6 * To evaluate the splenic response to SAR302503 at the end of Cycle 3 * To evaluate the effect of SAR302503 on the Janus kinase 2 (JAK2) V617F allele burden * To evaluate the safety and tolerability of SAR302503 in this population * To evaluate plasma concentrations of SAR302503 for population PK analysis, if warranted
Detailed description
The expected duration of the treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a 6-month (6-cycle) treatment period, and an EOT visit for subjects who will not continue the treatment after completing the 6 cycles of SAR302503, or discontinue the treatment early for any reasons as well as a follow-up visit which should occur 30 days after the last administration of SAR302503. Patients who continue to benefit clinically will be allowed to remain on study medication beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.
Interventions
DRUGSAR302503
Pharmaceutical form:capsule Route of administration: oral
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of PMF or Post-PV MF or Post-ET MF, according to the 2008 World Health Organization and IWG-MRT response criteria * Subjects who previously received Ruxolitinib treatment for PMF or Post-PV MF or Post-ET MF or PV or ET for at least 14 days (exposure of \<14 days is allowed for subjects who discontinued Ruxolitinib due to intolerability or allergy) and discontinued the treatment for at least 14 days prior to the first dose of SAR302503 * MF classified as Intermediate-1 with symptoms, Intermediate-2 or high-risk by Dynamic International Prognostic Scoring System (Passamonti et al., Blood 2010) * Spleen ≥5 cm below costal margin as measured by palpation * Male and female subjects ≥18 years of age * Signed written informed consent
Exclusion criteria
* Splenectomy * Eastern Cooperative Oncology Group (ECOG) performance status of \>2 before the first dose of SAR302503 at Cycle 1 Day1 * The following laboratory values within 14 days prior to the initiation of SAR302503: * Absolute Neutrophil Count (ANC) \<1.0 x 10exp9/L * Platelet count \<50 x 10exp9/L * Serum creatinine \>1.5 x Upper limit of normal (ULN) * Serum amylase and lipase \>1.5 x ULN * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN * Total bilirubin ≥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 * Subjects with known active (acute or chronic) Hepatitis A, B, or C; and Hepatitis B and C carriers * Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis \[NASH\]) * Subjects 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 subject has been disease-free for at least 5 years * Any chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), Anagrelide, 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 SAR302503; darbepoetin use within 28 days prior to initiation of SAR302503.The only chemotherapy allowed will be hydroxyurea within 1 day prior to initiation of SAR302503 * 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 SAR302503 The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 6 as measured by Magnetic Resonance Imaging (MRI) (or CT scan in subjects with contraindications for MRI) | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score using the modified MFSAF | 6 months |
| Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI) | 6 months |
| Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6 | 6 months |
| Response Rate at the end of Cycle 3, defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 3 as measured by MRI (or CT scan in subjects with contraindications for MRI) | 6 months |
| Percent change of spleen volume at the end of Cycles 3 and 6 from baseline as measured by MRI (or CT scan in subjects with contraindications for MRI) | 6 months |
| Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 | approximately 5 years |
| Plasma concentrations of SAR302503 | 4 months |
| The effect of SAR302503 on the JAK2V617F allele burden | 2 years |
Countries
Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Outcome results
None listed