Ruxolitinib vs Allogeneic SCT for Patients With Myelofibrosis According to Donor Availability

Study Overview
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Brief Summary
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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
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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.

Official Title
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Ruxolitinib Versus Allogeneic Stem Cell Transplantation for Patients With Myelofibrosis According to Donor Availability: A Prospective Phase II Trial (MMM 02 Study)

Conditions
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Bone Marrow Fibrosis

Intervention / Treatment
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* Procedure: Allogeneic stem cell transplantation
* Drug: Ruxolitinib continuous therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Treatment with Allogeneic Stem cell Transplantation after 3 months of Ruxolitinib induction therapy | Procedure: Allogeneic stem cell transplantation<br> <br> |
| Active Comparator: Arm B<br>Treatment with Ruxolitinib continuous therapy | Drug: Ruxolitinib continuous therapy<br> <br> * Other names: Jakavi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival | Compare to event free survival of patients at 3 years after allogeneic SCT and in Ruxolitinib continuous therapy in patients without a suitable donor | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spleen reduction | Ultrasound measurement Spleen size, reduction of Spleen size after 3 months Ruxolitinib induction therapy | 3 months | 
| Improvement of constitutional symptoms | Improvement of constitutional symptoms (Loose of weight and night sweat) after 3 months Ruxolitinib induction therapy, questionnaire, medical history | 3 months | 
| Improvement of bone marrow fibrosis | bone marrow histology, Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy | 3 months | 
| Acute graft-versus-host disease | Incidence of acute graft-versus-host disease on Day +100 after allogeneic SCT according to the Glucksberg scale revised by Przepiorka | Day +100 after allogeneic SCT | 
| Chronic graft-versus-host disease | 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 | 1, 2 and 3 years after allogeneic SCT | 
| Toxicity of Ruxolitinib | Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0 | till 3 years | 
| Toxicity of conditioning therapy | Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0 | till 3 years | 
| Relapse | Cumulative incidence of relapse at 3 years after allogeneic SCT | 3 years | 
| Disease-related mortality | Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous therapies | 3 years | 
| Non-relapsed mortality | Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy | 1 and 3 years | 
| Discontinuation rate | Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study) | 3 years | 
| Evaluation of Sorror Risk Score | Evaluation of Sorror Risk Score on outcome after allogeneic SCT | at baseline | 
| Chimerism on relapse | Chimerism Analyse, Impact of chimerism on relapse incidence after allogeneic SCT | 30d, 100d, 180 d, 1 year, 2 years and 3 years | 
| Bone marrow fibrosis regression | bone marrow histology, Evaluation of bone marrow fibrosis regression after allogeneic SCT at 30d, 100d, 1 year, and 3 years | 30d, 100d, 1 year, and 3 years | 
| Bone marrow fibrosis regression | bone marrow histology, Evaluation of bone marrow fibrosis regression after Ruxolitinib continuous therapy at 30d, 100d, 1 year and 3 years | 30d, 100d, 1 year and 3 years | 
| Evaluation of QOL (FACT-BMT) | 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 | baseline, at transplantation, +180d, +1 year, +2 years and +3 years | 
| Evaluation of QOL (MPN-SAF-TSS) | 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 | baseline, at transplantation, +180d, +1 year, +2 years and +3 years | 
| Evaluation of QOL (FACT-BMT) | 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 | baseline, confinement to Ruxolitinib continous therapy, +180d, +1 year, +2 years and +3 years | 
| Evaluation of QOL (MPN-SAF-TSS) | 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 | baseline, confinement to Ruxolitinib continous therapy, +180d, +1 year, +2 years and +3 years | 
| Overall Survival | Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suit-able donor | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelofibrosis, Myeloproliferative Disease