Primary myelofibrosis Polycythemia vera Essential thrombocytosis MedDRA version: 21.0 Level: LLT Classification code 10074689 Term: Post polycythemia vera myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10074690 Term: Post essential thrombocythemia myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20
Conditions
Interventions
Product Name: Pacritinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: pacritinib
CAS Number: 937272-79-2
Other descriptive name: PACRITINIB
Concentration unit: mg milligram(s)
Concentration
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Patients with a confirmed diagnosis of post-ET, post-PV or primary myelofibrosis (Appendix A) -Intermediate-2 or high-risk according to DIPSS plus (Appendix F) -Age 18-70 years inclusive -WHO performance status 0-2 (Appendix C) Platelet count = 25 × 109/L without platelet support within 2 weeks before study entry. -All men and women of childbearing potential must agree to use adequate contraception during the study -Written informed consent -Patient is capable of giving informed consent 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Patients who have been treated with pacritinib as their previous JAK2 inhibitor treatment cannot participate in this study. - Previous treatment with JAK2 inhbitors, other than pacritinib, is allowed with the exception of high dose ruxolitinib (above 10 mg BID). For these patients taper the dose to 10 mg BID or lower at least 2 weeks before pacritinib treatment is allowed. - Any GI or metabolic condition (e.g. inflammatory or chronic functional bowel disorder such as Crohn’s Disease, Inflammatory Bowel Disease, chronic diarrhea or constipation) that could interfere with absorption of oral medication - Left ventricular cardiac ejection fraction of = 45% by echocardiogram or multigated acquisition (MUGA) scan - Impaired liver and renal function, defined by liver transaminases (aspartate aminotransferase [AST]/serum glutamic oxaloacetic transaminase [SGOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]), >3 × the upper limit of normal (ULN) (AST/ALT >5 × ULN if transaminase elevation is related to MF), direct bilirubin >4× ULN, and creatinine clearance ? 40 ml/min. -Experimental treatment within four weeks before inclusion for PMF, Post-PV, or Post-ET MF -Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D) - Treatment with a potent strong CYP3A4 inhibitor or a strong cytochrome P450 (CYP450) inducer within the last 2 weeks - Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of =100 mg per day, within the last 2 weeks - New York Heart Association Class II, III, or IV congestive heart failure - QTc prolongation >450 ms as assessed by ECG and corrected by Federicia method or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval) - Significant recent bleeding history defined as NCI CTCAE grade =2 within the last 3 months, unless precipitated by an inciting event (e.g., surgery, trauma, injury) - Any history of CTCAE grade =2 non-dysrhythmia cardiac conditions within the last 6 months. Patients with asymptomatic grade 2 non-dysrhythmia cardiac conditions may be considered for inclusion, with the approval of the principal investigator, if stable and unlikely to affect patient safety - Any history of CTCAE grade =2 cardiac dysrhythmias within the last 6 months. Patients with non-QTc CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the principal investigator, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety -Patients with active, uncontrolled infections -Patients known to be HIV(human immunodeficiency virus)-positive -Active hepatitis A, B or C -History of active malignancy during the past 3 years, except basal carcinoma of the skin or stage 0 cervical carcinoma -Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.) -Pregnant or breastfeeding women -Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Improve allo-SCT transplant outcome using a uniform conditioning regimen and pacritinib pretreatment by means of the proportion of patients with a failure within 6 months post-transplant. Events that are considered a failure are: primary graft failure; secondary graft failure; acute GvHD grade 3-4; death whatever the cause is.;Secondary Objective: -Assess effect of pacritinib treatment on splenomegaly -Improve disease response by pacritinib treatment and allo-SCT -Determine proportion of patients receiving allo-SCT -Document safety and toxicity of pacritinib treatment before allo-SCT -Compare effect of treatment on marrow fibrosis by DCE-MRI scan -Evaluate efficacy of induction therapy determined as time to response -Determine time to red cell recovery after SCT -Determine progression free survival and overall survival from study inclusion and separately from allo-SCT in transplanted patients -Evaluate NRM (Non-Relapse -Mortality) from inclusion and separately after allo-SCT in transplanted patients -Determine effects on JAK2, calreticulin or mpl (allelic) burden before and after allo-SCT and donor (micro) chimerism -Summarize Quality-of-Life (QOL) during/after treatment using the MPN-SAF scoring tool -Determine effects on inflammatory cytokines -Determine prognostic value of additional molecular markers;Primary end point(s): Among the patients who received an allo-SCT, the proportion of patients with failure within or at D180 post-transplant. Events that are considered a failure are: -Primary graft failure; -Acute graft versus host disease grade 3-4; -Secondary graft failure; -Death, whatever the cause ;Timepoint(s) of evaluation of this end point: When data of the patients is available. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Adverse events • Proportion of patients receiving allo-SCT • Response rate (= PR) (see appendix B) • Progression free survival (PFS, i.e. time from either registration or allo-SCT until progression/relapse or death from any cause, whichever comes first) • Overall survival (OS) calculated from either registration or allo-SCT. Patients still alive or lost to follow up are censored at the date they were last known to be alive • Relapse mortality (RM), i.e. death due to the disease or after progression • Non-relapse mortality(NRM) • Quality of Life during/after treatment ;Timepoint(s) of evaluation of this end point: When the data of patients is available. | — |
Countries
Belgium, Netherlands
Contacts
Public ContactHOVON
Erasmus MC - HOVON
Outcome results
None listed