Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis MedDRA version: 18.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
CTI BioPharma Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1). Intermediate -1 or -2 high-risk (Passamonti et al 2010) PMF, PPV-MF, or PET-MF (Tefferi and Vardiman 2008; Barosi et al 2008) 2). Palpable splenomegaly = 5 cm below the lower costal margin (LCM) in midclavicular line by physical examination 3). Total Symptom Score (TSS) = 13 on the MPN-SAF-TSS 2.0, not including the inactivity question 4). Age = 18 years old 5). ECOG performance status 0-3 6). Peripheral blast count 500/µL 8). Patients who are platelet or red blood cell transfusion-dependent are eligible 9). Adequate liver and renal function, defined by liver transaminases (AST/SGOT and ALT/SGPT) = 3 × ULN (AST/ALT = 5 × ULN if transaminase elevation is related to MF), direct bilirubin = 4 x ULN, and creatinine = 2.5 mg/dL 10). At least 6 months from prior splenic irradiation 11). At least 12 months from prior 32P therapy 12). At least 1 week since prior treatment (most recent dose) with a potent cytochrome P450 3A4 (CYP3A4) inhibitor 13). At least 4 weeks since any experimental treatment for PMF, PPV-MF, or PET-MF 14). At least 2 weeks since any treatment for PMF, PPV-MF, or PET-MF 15). If fertile, willing to use effective birth control methods during the study. Women of childbearing potential must use highly effective methods (defined as those resulting in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 144
Exclusion criteria
Exclusion criteria: 1). Any gastrointestinal or metabolic condition that could interfere with absorption of oral medication 2). Life expectancy 450 ms or other factors that increase the risk for QT prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistant and refractory to correction], or family history of long QT interval syndrome). 13). Erythropoietic agent within 28 days prior to randomization 14). Thrombopoietic agent within 14 days prior to randomization 15). Known seropositivity for human immunodeficiency virus (HIV) 16). Known active hepatitis A, B, or C virus infection 17). Women who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of pacritinib with that of best available therapy (BAT) in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF); the efficacy measure for this analysis is the proportion of patients achieving a = 35% reduction in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan.;Secondary Objective: The key secondary objective is the proportion of patients with = 50% reduction in total symptom score (TSS)from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Asssessment Form (MPN -SAF TSS 2.0). Other secondary objectives are to compare pacritinib with BAT with respect to: 1. Proportion of patients with baseline platelet count < 100,000/µL achieving = 35% reduction in spleen volume from baseline to Week 24 as measured by MRI or CT scan 2. Proportion of patients with baseline platelet count < 100,000/µL achieving = 50% reduction in TSS from baseline to Week 24 3. Proportion of patients with baseline platelet count < 50,000/µL achieving = 35% reduction in spleen volume from baseline to Week 24 as measured by MRI or CT scan 4. Proportion of patients with baseline platelet count < 50,000/µL achieving = 50% reduction in TSS from baseline to Week 24;Primary end point(s): The primary endpoint for measurement of efficacy is the proportion of patients achieving a = 35% reduction in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan. ;Timepoint(s) of evaluation of this end point: MRI or CT assessments at: Screening and Wk 24 (exploratory evaluation only at weeks 12, 36, 48 and every 12 weeks). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoint is the proportion of patients with = 50% reduction in total symptom score (TSS) from baseline to Week 24 as measured by the Myleloproliferative Neoplasm Symptom Assessment Form (MPN-SAF TSS 2.0). ;Timepoint(s) of evaluation of this end point: Patients will complete the MPN-SAF TSS 2.0 daily for 7 to 10 consecutive days prior to start of study treatment and then daily from Day 1 through Week 48, or until patient discontinues study treatment, whichever occurs first. | — |
Countries
Australia, Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, New Zealand, Russian Federation, United Kingdom, United States
Contacts
Public ContactRegulatory Director
CTI Life Sciences Ltd.
Outcome results
None listed