Contributions
Abstract: PB1711
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
Background
Myelofibrosis (MF) is a serious and life-threatening myeloproliferative neoplasm (MPN) due to clonal proliferation of myeloid cells. Patients with MF and severe thrombocytopenia (platelet counts <50 x 109/L) are generally older and have more advanced disease with increased risk of bleeding, higher rates of anemia, higher rates of complex or unfavorable cytogenetics and shortened overall survival (~15 months) compared to those with higher platelet counts. Currently approved JAK inhibitors, ruxolitinib (RUX) and fedratinib (FED), were not studied in this high-risk population and neither drug has a recommended starting dose for the treatment of patients with severe thrombocytopenia. RUX often requires dose reductions for patients with platelet counts <100,000/mL, due to thrombocytopenia. Such dose reductions impair efficacy compared to higher doses. NCCN guidelines and ELN recommendations suggest enrollment in clinical trials for such patients due to limited therapeutic options. Pacritinib (PAC) is an oral JAK2/IRAK1 inhibitor that has demonstrated clinical activity in MF patients in prior phase 3 studies (PERSIST-1, PERSIST-2) and a phase 2 dose-finding study (PAC203), including in patients with severe thrombocytopenia.
Aims
The PACIFICA trial (NCT03165734) was designed to evaluate the efficacy and safety of PAC 200 mg twice daily (BID) vs physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia.
Methods
PACIFICA is a multinational, multicenter, randomized, controlled phase 3 trial of PAC vs P/C in adult patients with primary or secondary MF who are not candidates for stem cell transplant, with DIPSS intermediate- or high-risk disease, ECOG PS 0-2, and platelet counts <50 x 109/L, who have had limited prior JAK2 inhibitor treatment or are JAK2 inhibitor-naïve. Additional exclusion criteria include recent cardiac or hemorrhagic events, ejection fraction <50%, QTc >450 msec, or use of medications that increase the risk of hemorrhage or QT prolongation. Patients in the PAC arm receive continuous PAC 200 mg BID. Patients in the P/C arm receive one of the following agents as selected prior to randomization: low-dose ruxolitinib, danazol, corticosteroids, or hydroxyurea. The primary objective is to compare the efficacy of PAC vs P/C as assessed by the proportion of patients achieving a ≥35% spleen volume reduction (SVR) from baseline to week 24. Secondary objectives include comparisons of the proportion of patients achieving a ≥50% reduction in total symptom score (TSS) at week 24, overall survival, safety, and proportion of patients who self-assess as 'very much improved' or 'much improved' as measured by the Patient Global Impression of Change (PGIC). Tertiary endpoints include leukemia-free survival, alternative SVR analyses, hematologic improvement (transfusion independence and improvement in hemoglobin and platelet levels), fatigue improvement as measured by the PROMIS v.1.0 - Fatigue - Short form 7a, and changes in biomarkers and gene expression. The study will enroll approximately 348 patients in a 2:1 ratio (PAC to P/C). The primary analysis (for SVR) will be based on approximately 168 patients, while the secondary analyses (for TSS) will be based on the full sample size. PACIFICA is currently enrolling, with approximately 140 sites worldwide (US, Australia, Europe, Canada, Middle East, Asia, Russia).
Results
N/A
Conclusion
N/A
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Thrombocytopenia
Abstract: PB1711
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
Background
Myelofibrosis (MF) is a serious and life-threatening myeloproliferative neoplasm (MPN) due to clonal proliferation of myeloid cells. Patients with MF and severe thrombocytopenia (platelet counts <50 x 109/L) are generally older and have more advanced disease with increased risk of bleeding, higher rates of anemia, higher rates of complex or unfavorable cytogenetics and shortened overall survival (~15 months) compared to those with higher platelet counts. Currently approved JAK inhibitors, ruxolitinib (RUX) and fedratinib (FED), were not studied in this high-risk population and neither drug has a recommended starting dose for the treatment of patients with severe thrombocytopenia. RUX often requires dose reductions for patients with platelet counts <100,000/mL, due to thrombocytopenia. Such dose reductions impair efficacy compared to higher doses. NCCN guidelines and ELN recommendations suggest enrollment in clinical trials for such patients due to limited therapeutic options. Pacritinib (PAC) is an oral JAK2/IRAK1 inhibitor that has demonstrated clinical activity in MF patients in prior phase 3 studies (PERSIST-1, PERSIST-2) and a phase 2 dose-finding study (PAC203), including in patients with severe thrombocytopenia.
Aims
The PACIFICA trial (NCT03165734) was designed to evaluate the efficacy and safety of PAC 200 mg twice daily (BID) vs physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia.
Methods
PACIFICA is a multinational, multicenter, randomized, controlled phase 3 trial of PAC vs P/C in adult patients with primary or secondary MF who are not candidates for stem cell transplant, with DIPSS intermediate- or high-risk disease, ECOG PS 0-2, and platelet counts <50 x 109/L, who have had limited prior JAK2 inhibitor treatment or are JAK2 inhibitor-naïve. Additional exclusion criteria include recent cardiac or hemorrhagic events, ejection fraction <50%, QTc >450 msec, or use of medications that increase the risk of hemorrhage or QT prolongation. Patients in the PAC arm receive continuous PAC 200 mg BID. Patients in the P/C arm receive one of the following agents as selected prior to randomization: low-dose ruxolitinib, danazol, corticosteroids, or hydroxyurea. The primary objective is to compare the efficacy of PAC vs P/C as assessed by the proportion of patients achieving a ≥35% spleen volume reduction (SVR) from baseline to week 24. Secondary objectives include comparisons of the proportion of patients achieving a ≥50% reduction in total symptom score (TSS) at week 24, overall survival, safety, and proportion of patients who self-assess as 'very much improved' or 'much improved' as measured by the Patient Global Impression of Change (PGIC). Tertiary endpoints include leukemia-free survival, alternative SVR analyses, hematologic improvement (transfusion independence and improvement in hemoglobin and platelet levels), fatigue improvement as measured by the PROMIS v.1.0 - Fatigue - Short form 7a, and changes in biomarkers and gene expression. The study will enroll approximately 348 patients in a 2:1 ratio (PAC to P/C). The primary analysis (for SVR) will be based on approximately 168 patients, while the secondary analyses (for TSS) will be based on the full sample size. PACIFICA is currently enrolling, with approximately 140 sites worldwide (US, Australia, Europe, Canada, Middle East, Asia, Russia).
Results
N/A
Conclusion
N/A
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Thrombocytopenia