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.
Despite recent new therapeutic options, allogeneic Stem Cell Transplantation remains the only curative option in patients with Myelofibrosis. Therefore, optimalization of this therapy remains a major challenge. Improvement of the clinical condition of these patients, decreasing spleen size can be accomplished by JAK2 inhibitor treatment and might improve SCT outcome. In addition, selective JAK2 inhibitors might modulate GvHD which can also add to improved SCT outcome. Also, decreasing the burden/activity of the disease before allo-SCT might also improve final disease response. The first, limited, clinical data of ruxolitinib treatment before allo-SCT show controversial effects on the outcome of SCT. Therefore, additional prospective clinical trials have to be done to establish the role of JAK2 inhibition before allogeneic SCT. Since ruxolitinib has considerable myelosuppressive effects which might limit the clinical use in some MF patients, other selective JAK2 inhibitors might be useful in this setting. Pacritinib, as a JAK2/FLT3 inhibitor, has a very potent JAK2 inhibitory activity without myelosuppressive effects and might therefore be more suitable than ruxolitinib. The major possible side effects are gastro-intestinal and can be managed with medication. In several studies, pacritinib has shown to be effective in decreasing spleen size and has shown to improve clinical condition of patients. Therefore, this compound seems promising in improving the outcome of allo-SCT. Although pacritinib causes no inhibition of JAK1 activity and therefore might have limited effects in decreasing inflammatory response, this might also be of benefit since a "withdrawal syndrome" as has been described after cessation of ruxolitinib is not to be expected. With this trial, using pacritinib treatment before allo-SCT, the issue of improvement of SCT outcome will be investigated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
61
Patients receive up to 4 cycles of pacritinib before allo-SCT
BE-Antwerpen-ZNASTUIVENBERG
Antwerp, Belgium
BE-Gent-UZGENT
Ghent, Belgium
BE-Leuven-UZLEUVEN
Leuven, Belgium
BE-Roeselare-AZDELTA
Roeselare, Belgium
Proportion of patients receiving allo-SCT, with failure within or at day 180 post-transplant.
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
Time frame: 2 years
Adverse events
Adverse events will be monitored.
Time frame: 5 years
Progression free survival
Progression free survival as time between registration or SCT until progression/relapse or death from any cause
Time frame: 5 years
Overall survival
Over all survival, calculated from either registration or SCT.
Time frame: 5 years
Relapse mortality
Death due to the disease or after progression
Time frame: 5 years
Non-relapse mortality
Death not due to disease or relapse
Time frame: 5 years
Quality of life during and after treatment
Quality of life during and after treatment will be recorded by use of the MPN-SAF questionnaire. From a total of 27 questions, the scores (from 0 to 10) from the following 10 questions are added and subsequently averaged to come to a total quality of life score. * fatigue * satisfction after a meal * stomach complaints * not able to perform activities * concentration problems * night sweat * itch * bone pain * fever * sudden weight loss
Time frame: 5 years
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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
...and 2 more locations