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

Phase 2Active Not RecruitingNCT03333187

Universitätsklinikum Hamburg-Eppendorf87 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Bone Marrow Fibrosis

Interventions

Allogeneic stem cell transplantationPROCEDURE

Ruxolitinib continuous therapyDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (14)

Universitätsklinkum Aachen

Aachen, Germany

HELIOS Klinikum Berlin-Buch

Berlin, Germany

Universitätsklinikum Bonn

Bonn, Germany

Outcomes

Primary Outcomes

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

Time frame: 3 years

Secondary Outcomes

Spleen reduction

Ultrasound measurement Spleen size, reduction of Spleen size after 3 months Ruxolitinib induction therapy

Time frame: 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

Time frame: 3 months

Improvement of bone marrow fibrosis

bone marrow histology, Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy

Time frame: 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

Time frame: 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

Time frame: 1, 2 and 3 years after allogeneic SCT

Toxicity of Ruxolitinib

Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0

Time frame: till 3 years

Data from ClinicalTrials.gov

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Universitätsklinikum Düsseldorf

Düsseldorf, Germany

Universitätsklinkum Halle

Halle, Germany

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

Universitätsklinikum Jena

Jena, Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Germany

Johannes Wesling Klinikum Minden

Minden, Germany

Universitätsklinikum Münster

Münster, Germany

...and 4 more locations

Toxicity of conditioning therapy

Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0

Time frame: till 3 years

Relapse

Cumulative incidence of relapse at 3 years after allogeneic SCT

Time frame: 3 years

Disease-related mortality

Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous therapies

Time frame: 3 years

Non-relapsed mortality

Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy

Time frame: 1 and 3 years

Discontinuation rate

Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study)

Time frame: 3 years

Evaluation of Sorror Risk Score

Evaluation of Sorror Risk Score on outcome after allogeneic SCT

Time frame: at baseline

Chimerism on relapse

Chimerism Analyse, Impact of chimerism on relapse incidence after allogeneic SCT

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 3 years