Myelofibrosis, primary, post-ET, post PV-MF Allogeneic stem cell transplantation Myelofibrose Allogene stamceltransplantatie
Conditions
Interventions
Induction with 3-4 cycles pacritinib, followed by allo-SCT if suitable donor available. All patients will receive the same treatment.
Sponsors
HOVON
VU University Medical Center,
P.O.Box 7057
1007 MB Amsterdam
The Netherlands
tel: +31 20 4442124
tel: +31 20 4449086
Fax: +31 20 4443566
Eligibility
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 E) - Age 18-70 years inclusive - WHO performance status 0-2 (Appendix C) - At least 1 week since prior treatment (most recent dose) with a potent cytochrome P450 3A4 (CYP3A4) inhibitor - 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
Exclusion criteria
Exclusion criteria: - Previous treatment with JAK2 inhibitors within 2 weeks of study inclusion. Patients who have been treated with pacritinib as their previous JAK2 inhibitor treatment cannot participate in this study - Any GI or metabolic condition that could interfere with absorption of oral medication - Severe cardiac dysfunction (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease) - 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) - Significant hepatic dysfunction (total bilirubin ≥ 30 μmol/l or transaminases ≥ 3 times normal level, unless disease-related) - Severe neurological or psychiatric disease - Severe renal impairment (creatinine clearance < 40 ml/min) - 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 |
|---|---|
| Primary endpoint ♦ Proportion of patients receiving allo-SCT, with failure within or at day 180 post-transplant. Events that are considered a failure are: o Primary graft failure o Acute graft versus host disease grade 3-4 o Secondary graft failure o Death, from any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints ♦ 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 | — |
Contacts
Public ContactP.A.W. Boekhorst, te
Outcome results
None listed