Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis with Thrombocytopenia MedDRA version: 19.0 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 or high-risk PMF, PPV-MF, or PET-MF 2. Thrombocytopenia (platelet count =100,000/µL) at any time after signing informed consent 3. Informed consent may be signed up to 35 days prior to randomization 4. Palpable splenomegaly =5 cm below the LCM in midclavicular line by physical examination 5. Total Symptom Score (TSS) =13 on the MPN-SAF-TSS 2.0, not including the inactivity question 6. Age =18 years old 7. ECOG performance status 0 to 3 8. Peripheral blast count 500/µL 10. Patients who are platelet or RBC transfusion-dependent are eligible 11. 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 12. At least 6 months from prior splenic irradiation 13. At least 12 months from prior 32P therapy 14. At least 1 week since prior treatment (most recent dose) with a potent cytochrome P450 3A4 (CYP3A4) inhibitor 15. At least 2 weeks since receiving any treatment for PMF, PPV-MF, or PET-MF 16. If fertile, males and females must agree to use effective birth control methods during the study. 17. Willing to undergo and able to tolerate frequent MRI or CT assessments during the study 18. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument 19. Able to understand and willing to sign the informed consent form. 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 170 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 130
Exclusion criteria
Exclusion criteria: 1. Any gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral medication 2. Life expectancy less than 6 months 3. Prior treatment with more than 2 JAK2 inhibitors or pacritinib 4. There is no maximum cumulative prior JAK2 inhibitor treatment (approved or investigational) 5. Completed allogeneic stem cell transplantation (ASCT) or are eligible for and willing to complete ASCT 6. History of splenectomy or planning to undergo splenectomy 7. Uncontrolled intercurrent illness, including but not limited to ongoing active infection, psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements 8. Active bleeding requiring hospitalization during the screening period 9. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma 10. Inflammatory or chronic functional bowel disorder, such as Crohn’s disease, inflammatory bowel disease, chronic diarrhea, or constipation 11. Clinically symptomatic and uncontrolled cardiovascular disease 12. History of any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure 13. New York Heart Association Class III or IV congestive heart failure 14. Patients with National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion with the approval of the medical monitor if the arrhythmias are stable, asymptomatic and unlikely to affect patient safety. Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade =3, corrected QT interval (QTc) prolongation >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 persistent and refractory to correction], or family history of long QT interval syndrome). 15. Erythropoietic agent within 28 days prior to randomization 16. Thrombopoietic agent within 14 days prior to randomization 17. Known seropositivity for human immunodeficiency virus (HIV) 18. Known active hepatitis A, B, or C virus infection 19. Women who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the efficacy of two dose-schedule arm(s) of pacritinib (pooled once daily [QD] and twice-daily [BID] dosing arms) with that of best available therapy (BAT) in patients with thrombocytopenia and primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF). ;Secondary Objective: The secondary objectives are: 1. To compare the efficacy of QD pacritinib with that of BAT, as assessed by the proportion of patients achieving a = 35% reduction in spleen volume from baseline to Week 24 by MRI or CT and the proportion of patients achieving a = 50% reduction in the TSS from baseline to Week 24 on the MPN-SAF TSS 2.0. 2. To compare the efficacy of BID pacritinib with that of BAT, as assessed by the proportion of patients achieving a = 35% reduction in spleen volume from baseline to Week 24 by MRI or CT and the proportion of patients achieving a = 50% reduction in the TSS from baseline to Week 24 on the MPN-SAF TSS 2.0.;Primary end point(s): 1. 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; 2. the proportion of patients achieving a = 50% reduction in total symptom score (TSS) from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0).;Timepoint(s) of evaluation of this end point: 1. MRI or CT assessments at: Screening and Wk 24 (additional exploratory evaluation at weeks 12, 36, 48 and every 12 weeks). 2. TSS: assessed daily through week 48 of the study or until the patient discontinues study treatment, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not Applicable;Timepoint(s) of evaluation of this end point: Not Applicable | — |
Countries
Australia, Belgium, Canada, Czech Republic, France, Germany, Hungary, Italy, Netherlands, New Zealand, Russian Federation, United Kingdom, United States
Contacts
Public ContactVice President & EU General Manager
CTI Life Sciences Ltd.
Outcome results
None listed