Ruxolitinib Vs Allogeneic SCT for Patients with Myelofibrosis According to Donor Availability
- Conditions
- Bone Marrow Fibrosis
- Interventions
- Procedure: Allogeneic stem cell transplantation
- Registration Number
- NCT03333187
- Lead Sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Brief Summary
The present study will be a multicenter, prospective phase II-study comparing efficacy of allogeneic SCT for patients with myelofibrosis who have a suitable stem cell donor after a 3 months Ruxolitinib induction therapy with patients who lack a suitable stem cell donor and will continue to receive Ruxolitinib.
- Detailed Description
This study is a multicenter, prospective phase II-study compares efficacy of allogeneic SCT for patients with myelofibrosis who have a suitable stem cell donor after a 3 months Ruxolitinib induction therapy with patients who lack a suitable stem cell donor and will continue to receive Ruxolitinib.
In this study will further assess and compare the safety and efficacy of study treatments/ induction therapy in both study arms on spleen reduction, improvement of constitutional symptoms, QOL, toxicity, fibrosis regression, development of GvHD as well as chimerism, engraftment, relapse incidence, disease related mortality, outcome and overall survival.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 87
- Symptomatic primary myelofibrosis or myelofibrosis post polycythaemia vera or essential thrombocythemia stage intermediate 2- or high-risk according to IPSS or DIPSS [46] or intermediate 1-risk with high risk cytogenetics, other than normal karyotype, sole del 20q, del 13q, or sole+9, or transfusion-dependency
- Patients age: 18 - 70 years at time of inclusion (female and male)
- Patients understand and voluntarily sign an informed consent form
- Platelet count ≥ 50 x 109/L
- No prior Ruxolitinib treatment
- ECOG ≤ 2
-
Severe renal, hepatic, pulmonary or cardiac disease, such as:
- Total bilirubin, SGPT or SGOT > 3 times upper the normal level
- Left ventricular ejection fraction < 30 %
- Creatinine clearance < 30 ml/min
- DLCO < 35 % and/or receiving supplementary continuous oxygen
-
Positive serology for HIV
-
Pregnant or lactating women (positive serum pregnancy test)
-
Age < 18 and ≥ 71 years.
-
Uncontrolled invasive fungal infection at time of screening (baseline)
-
Serious psychiatric or psychological disorders
-
Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment
-
Transformation to AML
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Allogeneic stem cell transplantation Treatment with Allogeneic Stem cell Transplantation after 3 months of Ruxolitinib induction therapy Arm B Ruxolitinib continuous therapy Treatment with Ruxolitinib continuous therapy
- Primary Outcome Measures
Name Time Method Event free survival 3 years Compare to event free survival of patients at 3 years after allogeneic SCT and in Ruxolitinib continuous therapy in patients without a suitable donor
- Secondary Outcome Measures
Name Time Method Acute graft-versus-host disease Day +100 after allogeneic SCT Incidence of acute graft-versus-host disease on Day +100 after allogeneic SCT according to the Glucksberg scale revised by Przepiorka
Non-relapsed mortality 1 and 3 years Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy
Evaluation of QOL (FACT-BMT) baseline, confinement to Ruxolitinib continous therapy, +180d, +1 year, +2 years and +3 years Questionnaire, Evaluation of QOL (FACT-BMT) before Ruxolitinib induction therapy (= baseline), at confinement to Ruxolitinib continuous therapy and after confinement at 6 months, 1 year, 2 years and 3 years
Evaluation of QOL (MPN-SAF-TSS) baseline, confinement to Ruxolitinib continous therapy, +180d, +1 year, +2 years and +3 years Questionnaire, Evaluation of QOL (MPN-SAF-TSS) before Ruxolitinib induction therapy (= baseline), at confinement to Ruxolitinib continuous therapy and after confinement at 6 months, 1 year, 2 years and 3 years
Chimerism on relapse 30d, 100d, 180 d, 1 year, 2 years and 3 years Chimerism Analyse, Impact of chimerism on relapse incidence after allogeneic SCT
Bone marrow fibrosis regression 30d, 100d, 1 year and 3 years bone marrow histology, Evaluation of bone marrow fibrosis regression after Ruxolitinib continuous therapy at 30d, 100d, 1 year and 3 years
Overall Survival 3 years Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suit-able donor
Improvement of bone marrow fibrosis 3 months bone marrow histology, Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy
Toxicity of Ruxolitinib till 3 years Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0
Toxicity of conditioning therapy till 3 years Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0
Relapse 3 years Cumulative incidence of relapse at 3 years after allogeneic SCT
Evaluation of Sorror Risk Score at baseline Evaluation of Sorror Risk Score on outcome after allogeneic SCT
Spleen reduction 3 months Ultrasound measurement Spleen size, reduction of Spleen size after 3 months Ruxolitinib induction therapy
Improvement of constitutional symptoms 3 months Improvement of constitutional symptoms (Loose of weight and night sweat) after 3 months Ruxolitinib induction therapy, questionnaire, medical history
Chronic graft-versus-host disease 1, 2 and 3 years after allogeneic SCT Incidence of chronic graft-versus-host disease according to the NIH consensus criteria of Filipovich et al. at 1, 2 and 3 years after allogeneic SCT
Disease-related mortality 3 years Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous therapies
Discontinuation rate 3 years Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study)
Trial Locations
- Locations (14)
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinkum Aachen
🇩🇪Aachen, Germany
HELIOS Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Universitätsklinikum Jena
🇩🇪Jena, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Universitätsklinikum Münster
🇩🇪Munster, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
Klinikum Nürnberg
🇩🇪Nürnberg, Germany
Robert-Bosch-Krankenhaus Stuttgart
🇩🇪Stuttgart, Germany
Universitätsmedizin Tübingen
🇩🇪Tübingen, Germany
Universitätsklinkum Ulm
🇩🇪Ulm, Germany
Universitätsklinkum Halle
🇩🇪Halle (Saale), Germany