Pacritinib: Patients receive up to 4 cycles of pacritinib before allo-SCT
Study summary
The only curative treatment for patients with myelofibrosis (MF) is allogeneic stem cell transplantation (SCT). Treatment with JAK2 inhibitors like pacritinib improves condition of MF patients, decreases spleen size and might diminish graft-versus-host disease (GvHD), thereby improving the outcome of SCT.
Eligibility
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
Inclusion Criteria:
* Patients with a confirmed diagnosis of post-ET, post-PV or primary myelofibrosis
* Intermediate-2 or high-risk according to DIPSS plus (Appendix E)
* Age 18-70 years inclusive
* WHO performance status 0-2 (Appendix C)
* 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:
* 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 (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.
* Impaired coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (APTT)\>1.5 x ULN.
* 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
Primary outcome measure(s)
Proportion of patients receiving allo-SCT, with failure within or at day 180 post-transplant. — 2 years Failure can be defined by one of the following parameters:
* Primary graft failure
* Acute graft versus host disease grade 3-4
* Secondary graft failure
* Death, from any cause
Trial sites (12)
Facility
City
Region
Status
BE-Antwerpen-ZNASTUIVENBERG
Antwerp
Belgium
BE-Gent-UZGENT
Ghent
Belgium
BE-Leuven-UZLEUVEN
Leuven
Belgium
BE-Roeselare-AZDELTA
Roeselare
Belgium
NL-Amsterdam-AMC
Amsterdam
Netherlands
NL-Amsterdam-VUMC
Amsterdam
Netherlands
NL-Groningen-UMCG
Groningen
Netherlands
NL-Maastricht-MUMC
Maastricht
Netherlands
NL-Nijmegen-RADBOUDUMC
Nijmegen
Netherlands
NL-Rotterdam-EMCDANIEL
Rotterdam
Netherlands
NL-Rotterdam-ERASMUSMC
Rotterdam
Netherlands
NL-Utrecht-UMCUTRECHT
Utrecht
Netherlands
More Stichting Hemato-Oncologie voor Volwassenen Nederland trials in Belgium
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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