Bone Marrow Fibrosis
Conditions
Keywords
Myelofibrosis, Myeloproliferative Disease
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.
Interventions
PROCEDUREAllogeneic stem cell transplantation
DRUGRuxolitinib continuous therapy
Sponsors
Novartis
Clinical Trial Center North (CTC North GmbH & Co. KG)
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Treatment A (only with a suitable stem cell donor): Allogeneic SCT after 3 months of Ruxolitinib induction therapy Treatment B: Ruxolitinib continuous therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. 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 2. Patients age: 18 - 70 years at time of inclusion (female and male) 3. Patients understand and voluntarily sign an informed consent form 4. Platelet count ≥ 50 x 109/L 5. No prior Ruxolitinib treatment 6. ECOG ≤ 2
Exclusion criteria
1. 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 2. Positive serology for HIV 3. Pregnant or lactating women (positive serum pregnancy test) 4. Age \< 18 and ≥ 71 years. 5. Uncontrolled invasive fungal infection at time of screening (baseline) 6. Serious psychiatric or psychological disorders 7. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment 8. Transformation to AML
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Improvement of bone marrow fibrosis | 3 months | bone marrow histology, Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy |
| 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 |
| 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 |
| Disease-related mortality | 3 years | Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous therapies |
| 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 |
| Discontinuation rate | 3 years | Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study) |
| Evaluation of Sorror Risk Score | at baseline | Evaluation of Sorror Risk Score on outcome after allogeneic SCT |
| 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 allogeneic SCT at 30d, 100d, 1 year, and 3 years |
| Evaluation of QOL (FACT-BMT) | baseline, at transplantation, +180d, +1 year, +2 years and +3 years | Questionnaire, Evaluation of QOL (FACT-BMT) before Ruxolitinib induction therapy (= baseline), at transplantation, and after transplantation at 6m, 1 year, 2 years and 3 years |
| Evaluation of QOL (MPN-SAF-TSS) | baseline, at transplantation, +180d, +1 year, +2 years and +3 years | Questionaire, Evaluation of QOL (MPN-SAF-TSS) before Ruxolitinib induction therapy (= baseline), at transplantation, and after transplantation at 6m, 1 year, 2 years 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 |
| Non-relapsed mortality | 1 and 3 years | Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy |
Countries
Germany
Outcome results
None listed