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    Clinical Trial Results:
    Ruxolitinib versus allogeneic stem cell transplantation for patients with myelofibrosis according to donor availability: A prospective phase II trial (MMM 02 study)

    Summary
    EudraCT number
    		 2014-005210-28
    Trial protocol
    		 DE  
    Global end of trial date
    07 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Oct 2026
    First version publication date
    18 Oct 2026
    Other versions
    Summary report(s)
    		 Summary results

    Trial information

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    Trial identification
    Sponsor protocol code
    MMM02Study
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03333187
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University Medical Center Hamburg-Eppendorf
    Sponsor organisation address
    Martinistr. 52, Hamburg, Germany, 20246
    Public contact
    Study Investigator, University Medical Center Hamburg-Eppendorf , bmt@uke.de
    Scientific contact
    Study Investigator, University Medical Center Hamburg-Eppendorf , bmt@uke.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Oct 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Oct 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare efficacy in terms of event free survival 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.
    Protection of trial subjects
    The responsible Investigator ensured that this study was conducted in conformity with the declaration of Helsinki (latest version) and the national laws and regulations. The protocol had been written and the study was conducted according to the ICH Harmonized Tripartite Guideline for Good Clinical Practice, issued by the European Union. The responsible Ethics Committee and the Competent Authority approvals were obtained before starting the trial. Among other documents the study protocol, the patient information and the informed consent form were initially submitted to the responsible Ethics Committees to request for approval (favorable opinion). In parallel the necessary documents were initially submitted to the Competent Authority (Paul Ehrlich Institute, PEI) for approval. If any amendments had been necessary during study conduct, they were submitted in the same way. The beginning (initiation visit) and the end (last patient’s last visit) of this trial and all amendments were announced to the appropriated local authority for each study site in accordance with § 67 (1) AMG. The approval of both, the Ethics Committee and the PEI for each study site was obtained prior to the start of the study. Copies of the original approval documents were immediately sent to the Sponsor and were included in the study report. A list of members of the independent Ethics Committee had also been provided with the final report.
    Background therapy
    		 Ruxolitinib was prescribed and used as directed in the current Summary of Product Characteristics (SmPC). After enrollment the patient started with Ruxolitinib 2 x 15 mg daily if platelet count was between 100 and 200 x 10E9/L and with 2 x 20 mg daily if platelet count was more than 200 x 10E9/L. If platelet count was between 50 and 100 x 10E9/L the starting dose should be 2 x 5 mg daily. If platelet count dropped to less than 50 x 10E9/L or neutrophil count to less than 0.5 x 10E9/L Ruxolitinib medication should be discontinued until cytopenia was resolved. If after 3 months of treatment no compatible stem cell donor had been found, Ruxolitinib was continued until disease progression or unacceptable side effects as toxicities defined per NCI CTCAE.
    Evidence for comparator
    		 Ruxolitinib continuous therapy: standard treatment for patients with myelofibrosis. The comparator is the current standard therapy, which is well established and supported by clinical guidelines and evidence from multiple studies.
    Actual start date of recruitment
    21 Dec 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 83
    Worldwide total number of subjects
    83
    EEA total number of subjects
    83
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    60
    From 65 to 84 years
    23
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 21.12.2016: first study site active; first patient consented: 09.01.2017; end of recruitment phase 31.05.2021. This study was conducted in Germany. 14 study sites were involved.

    Pre-assignment
    Screening details
    		 All patients with myelofibrosis (intermediate 2- or high-risk or intermediate 1- with high-risk cytogenetics, or transfusion-dependency, or thrombocytopenia) from each participating center, who are 18 to 70 years of age, were enrolled.

    Period 1
    Period 1 title
    Entered Population
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Entered population (EP)/ Pre-assignment
    Arm description
    		 Entered population (EP) includes all enrolled patients who were eligible to enter the study, whether treated or not. It is used for disposition displays, demographics and baseline characteristics.
    Arm type
    		 Entered population before randomisation

    Investigational medicinal product name
    human allogeneic hematopoietic stem cells (allo-HSC)
    Investigational medicinal product code
    NA
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    in accordance with routine care

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    SUB32897
    Other name
    Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10 - 40 mg milligram(s)

    Number of subjects in period 1
    		Entered population (EP)/ Pre-assignment
    Started
    83
    Completed
    71
    Not completed
    12
         Donor is from antother EU Member State
    5
         Terminated during induction therapy
    7
    Period 2
    Period 2 title
    Treatment Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Treatment A: Allogeneic SCT
    Arm description
    		 Allogeneic SCT after 3 months of Ruxolitinib induction therapy
    Arm type
    		 Experimental

    Investigational medicinal product name
    human allogeneic hematopoietic stem cells (allo-HSC)
    Investigational medicinal product code
    NA
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    in accordance with routine care

    Arm title
    		 Treatment B: Ruxolitinib continuous therapy
    Arm description
    		 Treatment B: Ruxolitinib induction therapy followed by Ruxolitinib continuous therapy
    Arm type
    		 Active comparator

    Investigational medicinal product name
    human allogeneic hematopoietic stem cells (allo-HSC)
    Investigational medicinal product code
    NA
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    in accordance with routine care

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    SUB32897
    Other name
    Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10 - 40 mg milligram(s)

    Number of subjects in period 2
    		Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Started
    57
    14
    Completed
    39
    4
    Not completed
    18
    10
         Patient´s decision
    1
    -
         Toxicity
    -
    1
         Other
    8
    4
         Disease Progression
    9
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Entered Population
    Reporting group description
    		 -

    Reporting group values
    		 Entered Population Total
    Number of subjects
    		 83 83
    Age categorical
    Units: Subjects
        24 - 70 years
    		 83 83
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58 ( 9.7 ) -
    Gender categorical
    Units: Subjects
        Female
    		 26 26
        Male
    		 57 57
    Disease classification IPSS
    Units: Subjects
        High-risk
    		 5 5
        Intermediate 1
    		 6 6
        Intermediate 2
    		 17 17
        Missing
    		 55 55
    Disease classification DIPSS
    Units: Subjects
        High (5-6)
    		 9 9
        Intermediate 1 - risk (1-2)
    		 14 14
        Intermediate 2 - risk (3-4)
    		 51 51
        Missing
    		 9 9
    Disease History - Type of Myelofibrosis
    Units: Subjects
        Primary Myelofibrosis (PMF)
    		 59 59
        Post Essential Thrombocythemia Myelofibrosis (Post
    		 14 14
        Post Polycythemia Vera Myelofibrosis (Post PV MF)
    		 10 10

    End points

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    End points reporting groups
    Reporting group title
    Entered population (EP)/ Pre-assignment
    Reporting group description
    		 Entered population (EP) includes all enrolled patients who were eligible to enter the study, whether treated or not. It is used for disposition displays, demographics and baseline characteristics.
    Reporting group title
    Treatment A: Allogeneic SCT
    Reporting group description
    		 Allogeneic SCT after 3 months of Ruxolitinib induction therapy

    Reporting group title
    Treatment B: Ruxolitinib continuous therapy
    Reporting group description
    		 Treatment B: Ruxolitinib induction therapy followed by Ruxolitinib continuous therapy

    Primary: Event free survival (EFS) at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suitable donor.

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    End point title
    		 Event free survival (EFS) at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suitable donor. [1]
    End point description
    Event-free survival (EFS) was defined as the probability of being alive with no sign of relapse or progression and without changing therapy. The associated time span was defined as the interval from Day 0 (inclusion into the study, that is, assessment date of eligibility) to relapse or progression or death due to any cause or change of therapy whatever comes first. A progress, a relapse, death from any cause and a change of therapy will be considered as an event. Patients without an event are censored at the last time without indication of an event. The primary efficacy analysis was performed in the Full Analysis Set. The asymptotic Z-test will be used to test for differences in the 3 year EFS rates measured by Kaplan-Meier method. Cox model, log-rank test and Kaplan-Meier survival analysis was used to determine the hazard ratio, p-values, risk estimates and related measures for time-to-event endpoints (event-free survival, overall survival).
    End point type
    Primary
    End point timeframe
    3 years
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Please refer to: End point description
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57
    14
    Units: Survival probability
        number (not applicable)
    0.744
    0.144
    Attachments
    		 Event free survival
    No statistical analyses for this end point

    Secondary: Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suitable donor

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    End point title
    		 Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suitable donor
    End point description
    Overall survival at 3 years will was compared between the two treatment groups “SCT” and “ContRuxo” in the same way as primary analysis of the primary endpoint. Overall survival (OS) was defined as the probability of surviving a specific time. Survival time was defined as the time span from Day 0 to death due to any cause. Patients alive are censored at their last follow-up. Population: FAP
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57
    14
    Units: days
        median (full range (min-max))
    1231 (173 to 1439)
    1176 (169 to 1253)
    Attachments
    		 Overall survival
    No statistical analyses for this end point

    Secondary: Spleen reduction after 3 months Ruxolitinib induction therapy (the effect on spleen size will be analyzed according to the pretreatment versus no pretreatment of Ruxolitinib prior to study inclusion)

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    End point title
    		 Spleen reduction after 3 months Ruxolitinib induction therapy (the effect on spleen size will be analyzed according to the pretreatment versus no pretreatment of Ruxolitinib prior to study inclusion)
    End point description
    Change in percentage of patients with spleen response (spleen volume reduction) from before Ruxolitinib induction therapy to after 3 months from start of Ruxolitinib induction therapy was tested by McNemar’s test. Population: SP Analysis not conducted since spleen response not determined at before Ruxolitinib induction therapy
    End point type
    Secondary
    End point timeframe
    3 month
    End point values
    		 Entered population (EP)/ Pre-assignment
    Number of subjects analysed
    83 [2]
    Units: Number of patients
    0
    Notes
    [2] - Analysis not conducted since spleen response not determined at before Ruxolitinib induction therapy.
    No statistical analyses for this end point

    Secondary: Improvement of constitutional symptoms (Loose of weight and night sweat) after 3 months Ruxolitinib induction therapy (the effect on constitutional symptoms will be analyzed according to the pretreatment versus no pretreatment of Ruxolitinib prior to stud

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    End point title
    		 Improvement of constitutional symptoms (Loose of weight and night sweat) after 3 months Ruxolitinib induction therapy (the effect on constitutional symptoms will be analyzed according to the pretreatment versus no pretreatment of Ruxolitinib prior to stud
    End point description
    Change in constitutional symptoms from before Ruxolitinib induction therapy to after 3 months from start of Ruxolitinib induction therapy, in particular a) Change in weight was tested by a paired t-test and b) Change in number of sweats per night was tested by Wilcoxon signed-rank test (number of night sweats is defined as a score (0=absent, 1, 2, …, 10, 11=worst imaginable) Population: SP
    End point type
    Secondary
    End point timeframe
    3 month
    End point values
    		 Entered population (EP)/ Pre-assignment
    Number of subjects analysed
    74 [3]
    Units: Kg
    arithmetic mean (confidence interval 95%)
        Change in weigh
    2.443 (1.605 to 3.281)
    Attachments
    		 Change in constitutional symptoms
    Notes
    [3] - Safety Population
    No statistical analyses for this end point

    Secondary: Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy

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    End point title
    		 Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy
    End point description
    Change in grading of bone marrow fibrosis from before Ruxolitinib induction therapy to after 3 months from start of Ruxolitinib induction therapy was tested by Wilcoxon signed-rank test (there are 4 gradings of bone marrow fibrosis: MF-0, MF-1, MF-2, MF-3, MF-4) Population: SP
    End point type
    Secondary
    End point timeframe
    3 month
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    37 [4]
    8 [5]
    Units: Number of patients
        Baseline MF-1
    1
    1
        Baseline MF-2
    13
    4
        Baseline MF-3
    23
    3
        After 3 month of induction MF-1
    3
    1
        After 3 month of induction MF-2
    13
    3
        After 3 month of induction MF-3
    21
    4
    Attachments
    		 Change in grading of bone marrow
    Notes
    [4] - Safety Population
    [5] - Safety Population
    No statistical analyses for this end point

    Secondary: Incidence of acute graft-versus-host disease on Day +100 after allogeneic SCT according to the Glucksberg scale revised by Przepiorka et al.

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    End point title
    		 Incidence of acute graft-versus-host disease on Day +100 after allogeneic SCT according to the Glucksberg scale revised by Przepiorka et al.
    End point description
    Incidence of acute graft-versus-host disease on Day +100 after allogeneic SCT according to the Glucksberg scale revised by Przepiorka et al. was evaluated by means of estimating cumulative incidence functions. Cumulative incidence functions was estimated for the competing events • any acute GvHD and • death before any acute GvHD and if possible cumulative incidence functions was estimated for the competing events • acute GvHD of grade 0-II and • death before acute GvHD of grade 0-II and if possible cumulative incidence functions was estimated for the competing events • acute GvHD of grade III-IV and • death before acute GvHD of grade III-IV. Population: FAP_SCT
    End point type
    Secondary
    End point timeframe
    day + 100
    End point values
    		 Treatment A: Allogeneic SCT
    Number of subjects analysed
    57
    Units: Proportion
    number (confidence interval 95%)
        Any acute GvHD
    0.411 (0.280 to 0.536)
        Death before any acute GcHD
    0 (0 to 0)
    Attachments
    		 actute GVHD
    No statistical analyses for this end point

    Secondary: 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

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    End point title
    		 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
    End point description
    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. For chronic GvHD relapse and death are competing events. Cumulative incidence functions will be estimated for the competing events • any chronic GvHD • relapse before any chronic GvHD • death before any chronic GvHD Population: FAP_SCT
    End point type
    Secondary
    End point timeframe
    1, 2 and 3 years after allogeneic SCT
    End point values
    		 Treatment A: Allogeneic SCT
    Number of subjects analysed
    57
    Units: Proportion
    number (confidence interval 95%)
        1 year: any chronic GvHD
    0.499 (0.358 to 0.625)
        1 year: relapse before any chronic GvHD
    0.091 (0.033 to 0.186)
        1 year: death before any chronic GvHD
    0.037 (0.007 to 0.115)
        2 years: Any chronic GvHD
    0.575 (0.429 to 0.696)
        2 years: relapse before any chronic GvHD
    0.091 (0.033 to 0.186)
        2 years: death before any chronic gvHD
    0.037 (0.007 to 0.115)
        3 years: any chronic GvHD
    0.634 (0.486 to 0.750)
        3 years: relapse before any chronic GvHD
    0.151 (0.069 to 0.262)
        3 years: death before any chronic GvHD
    0.037 (0.007 to 0.115)
    Attachments
    		 Incidence of chronic graft-versus-host disease
    No statistical analyses for this end point

    Secondary: Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0

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    End point title
    		 Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0
    End point description
    Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0 will be evaluated as a safety endpoint in section 10.8.3 on the SP population.
    End point type
    Secondary
    End point timeframe
    study period
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57 [6]
    14 [7]
    Units: patients
        median (inter-quartile range (Q1-Q3))
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [6] - Not provided. Please refer to SAE section.
    [7] - Not provided. Please refer to SAE section.
    No statistical analyses for this end point

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

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    End point title
    		 Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0
    End point description
    Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0 will be evaluated as a safety endpoint in section 10.8.3 on the SP population.
    End point type
    Secondary
    End point timeframe
    study period
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57 [8]
    14 [9]
    Units: patients
        median (inter-quartile range (Q1-Q3))
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [8] - Not provided. Please refer to SAE section.
    [9] - Not provided. Please refer to SAE section.
    No statistical analyses for this end point

    Secondary: Cumulative incidence of relapse at 3 years after allogeneic SCT

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    End point title
    		 Cumulative incidence of relapse at 3 years after allogeneic SCT
    End point description
    Cumulative incidence of relapse at 3 years after allogeneic SCT Cumulative incidence of relapse was defined as the probability of having had a relapse before or at time t.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57
    14
    Units: Proportion
        number (not applicable)
    0.183
    0.563
    Attachments
    		 Cumulative incidence of relapse
    No statistical analyses for this end point

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

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    End point title
    		 Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous therapies
    End point description
    Disease-related mortality at 3 years was compared between the two treatment groups “SCT” and “ContRuxo” in the same way as the primary endpoint. A CRF field (with the following two checkboxes: disease related and non-disease related) will ask for the reason of death. Depending on this the cumulative distribution functions for the two competing events will be calculated. Patients alive was censored at last contact similar to all other analyses. Population: FAP
    End point type
    Secondary
    End point timeframe
    3 years after allogeneic SCT
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57
    14
    Units: Proportion
    number (not applicable)
        Disease-related mortality
    0.093
    0.171
        Relapse
    0.099
    0.400
    Attachments
    		 Incidence of Disease-related mortality
    No statistical analyses for this end point

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

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    End point title
    		 Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy
    End point description
    Non-relapse mortality Non-relapse mortality (NRM) was defined as the probability of dying without previous occurrence of a relapse. The associated time span was defined as the interval from Day 0 to death without previous relapse. Patients alive without relapse are censored at last contact. Relapse was considered a competing event. A relapse (first relapse) was experienced for a patient • in the “SCT”-arm if = Relapse or Progressive disease • in the “ContRuxo”-arm if change of therapy is documented as a valid date in CRF-form called "Ruxo-Discontinuation".
    End point type
    Secondary
    End point timeframe
    1 year and 3 years after allogeneic SCT and Ruxolitinib continuous therapy
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57
    14
    Units: Proportion
    number (not applicable)
        100 days non-relapse mortatlity
    0.000
    0.000
        100 days Relapse
    0.018
    0.214
        1 year non-relapse mortality
    0.055
    0.000
        1 year relapse
    0.107
    0.476
    Attachments
    		 Incidence of non-relapse mortality
    No statistical analyses for this end point

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

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    End point title
    		 Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study)
    End point description
    Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study) were compared between the two treatment groups “SCT” and “ContRuxo” descriptively by means of Kaplan Meier curves. The associated time span was defined as the interval from Day 0 (inclusion into the study, that is, assessment date of eligibility) to study discontinuation (documented in the End-of-study form). Patients not having discontinued the study were censored at their last follow-up. Population: FAP
    End point type
    Secondary
    End point timeframe
    3 years after start of continuous Ruxolitinib therapy (End of study)
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57
    14
    Units: Proportion
        number (not applicable)
    0.789
    0.714
    Attachments
    		 Discontinuation rate
    No statistical analyses for this end point

    Secondary: Evaluation of Sorror Risk Score on outcome after allogeneic SCT

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    End point title
    		 Evaluation of Sorror Risk Score on outcome after allogeneic SCT
    End point description
    The impact of the comorbidity-index (HCT-CI) according to Sorror on event-free survival were be assessed by a Cox model with comorbidity-index HCT-CI as continuous covariate and treatment as categorical covariate. Population: FAP
    End point type
    Secondary
    End point timeframe
    after allogeneic SCT
    End point values
    		 Entered population (EP)/ Pre-assignment
    Number of subjects analysed
    71 [10]
    Units: Hazard Ratio
    number (confidence interval 95%)
        SCT
    0.289 (0.115 to 0.726)
        HCT-CI
    1.391 (1.119 to 1.729)
    Attachments
    		 Evaluation of Sorror Score
    Notes
    [10] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Impact of chimerism on relapse incidence after allogeneic SCT

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    End point title
    		 Impact of chimerism on relapse incidence after allogeneic SCT
    End point description
    To assess the impact of chimerism on incidence of relapse after allogeneic SCT. Complete donor chimerism was defined as more than 95% of haematopoietic cells derived from the donor, that is, if for a patient i_chim-bone-res >= 95% in the form f_chimerism then this patient is considered to be a patient with “complete chimerism”. Else if i_chim-bone-res < 95% then this patient is considered to be a patient with “mixed chimerism”. The frequency of SCT-patients with complete and mixed chimerism were shown in a table. Additionally, the frequency of SCT-patients with complete chimerism and relapse as well as patients with mixed chimerism and relapse were summarised in a table.
    End point type
    Secondary
    End point timeframe
    Follow-up after SCT
    End point values
    		 Treatment A: Allogeneic SCT
    Number of subjects analysed
    57
    Units: Number of patients
        Patient chimerism status: Complete chimerism
    30
        Patient chimerism status: Mixed chimerism
    3
        Patient chimerism status: Missing
    24
        Patient with complete chimerism and relapse: yes
    4
        Patient with complete chimerism and relapse: no
    35
        Patient with complete chimerism and relapse: miss.
    18
        Patient with mixed chimerism and relapse: no
    39
        Patient with mixed chimerism and relapse: missing
    18
    Attachments
    		 Impact of chimerism
    No statistical analyses for this end point

    Secondary: Evaluation of bone marrow fibrosis regression after allogeneic SCT at 30 days, 100 days, 1 year, and 3 years

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    End point title
    		 Evaluation of bone marrow fibrosis regression after allogeneic SCT at 30 days, 100 days, 1 year, and 3 years
    End point description
    Evaluation of grading of bone marrow fibrosis from baseline to after allogeneic SCT + 30d after allogeneic SCT + 100d after allogeneic SCT + 1 year after allogeneic SCT + 3 years were shown by frequency tables and descriptive statistics (n Mean standard deviation (SD) coefficient of variation (CV) Min Median Max) by treatment group and visit. (There are 4 gradings of bone marrow fibrosis: MF-0, MF-1, MF-2, MF-3, MF-4). Population: FAP
    End point type
    Secondary
    End point timeframe
    after allogeneic SCT at 30 days, 100 days, 1 year, and 3 years
    End point values
    		 Treatment A: Allogeneic SCT
    Number of subjects analysed
    57
    Units: Number of patients
        Allogeneic SCT day +30 days: MF-0
    5
        Allogeneic SCT day +30 days: MF-1
    9
        Allogeneic SCT day +30 days: MF-2
    10
        Allogeneic SCT day +30 days: MF-3
    9
        Allogeneic SCT day +30 days: Missing
    24
        Allogeneic SCT day +100 days: MF-0
    6
        Allogeneic SCT day +100 days: MF-1
    11
        Allogeneic SCT day +100 days: MF-2
    7
        Allogeneic SCT day +100 days: MF-3
    8
        Allogeneic SCT day +100 days: Missing
    25
        Allogeneic SCT day +1 year: MF-0
    18
        Allogeneic SCT day +1 year: MF-1
    4
        Allogeneic SCT day +1 year: MF-2
    3
        Allogeneic SCT day +1 year: MF-3
    3
        Allogeneic SCT day +1 year: Missing
    29
        Allogeneic SCT day +3 years: MF-0
    8
        Allogeneic SCT day +3 years: MF-1
    2
        Allogeneic SCT day +3 years: Missing
    46
    Attachments
    		 Evaluation of bone marrow fibrosis regression
    No statistical analyses for this end point

    Secondary: Evaluation of bone marrow fibrosis regression after Ruxolitinib continuous therapy at 30 days, 100 days, 1 year and 3 years

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    End point title
    		 Evaluation of bone marrow fibrosis regression after Ruxolitinib continuous therapy at 30 days, 100 days, 1 year and 3 years
    End point description
    Evaluation of grading of bone marrow fibrosis from baseline to after 2 months of Ruxolitinib continuous therapy after 4 months of Ruxolitinib continuous therapy after 1 year of Ruxolitinib continuous therapy after 3 years of Ruxolitinib continuous therapy were shown by frequency tables and descriptive statistics (n Mean standard deviation (SD) coefficient of variation (CV) Min Median Max) by treatment group and visit. (There are 4 gradings of bone marrow fibrosis: MF-0, MF-1, MF-2, MF-3, MF-4). Population: FAP
    End point type
    Secondary
    End point timeframe
    after Ruxolitinib continuous therapy at 30 days, 100 days, 1 year and 3 years
    End point values
    		 Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    14
    Units: Number of patients
        After 2 months of Ruxo. con. therapy: MF-1
    1
        After 2 months of Ruxo. con. therapy: MF-2
    1
        After 2 months of Ruxo. con. therapy: MF-3
    2
        After 2 months of Ruxo. con. therapy: Missing
    10
        After 4 months of Ruxo. con. therapy: MF-3
    3
        After 4 months of Ruxo. con. therapy: missing
    11
        After 1 year of Ruxo. con. therapy: MF-1
    1
        After 1 year of Ruxo. con. therapy: missing
    13
        After 3 year of Ruxo. con. therapy: missing
    14
    Attachments
    		 Evaluation of bone marrow fibrosis regression
    No statistical analyses for this end point

    Secondary: Evaluation of QoL (FACT-BMT) and QoL Myeloproliferated neoplasm (MPN) before Ruxolitinib induction therapy (= baseline), at transplantation, and after transplantation at 6 months, 1 year, 2 years and 3 years

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    End point title
    		 Evaluation of QoL (FACT-BMT) and QoL Myeloproliferated neoplasm (MPN) before Ruxolitinib induction therapy (= baseline), at transplantation, and after transplantation at 6 months, 1 year, 2 years and 3 years
    End point description
    The Quality of Life Score Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) before Ruxolitinib induction therapy (= baseline), after 3 months of Ruxolitinib induction therapy at transplantation (for “SCT” arm) at 6 months 1 year 2 years and 3 years were evaluated with frequency tables by study arms (“ContRuxo”, “SCT”, “Not Assigned”) and visit. Population: FAP
    End point type
    Secondary
    End point timeframe
    before Ruxolitinib induction therapy (= baseline), at transplantation, and after transplantation at 6 months, 1 year, 2 years and 3 years
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57
    14
    Units: Number of patients
        Before induction therapy: Score 0
    3
    0
        Before induction therapy: Score 1
    5
    2
        Before induction therapy: Score 2
    11
    2
        Before induction therapy: Score 3
    8
    0
        Before induction therapy: Score 4
    10
    2
        Before induction therapy: Score 5
    10
    4
        Before induction therapy: Score 6
    5
    1
        Before induction therapy: Score 7
    1
    2
        Before induction therapy: Score 8
    1
    0
        Before induction therapy: Score NA
    1
    1
        Before induction therapy: missing
    2
    0
        After 3 Month induction therapy: Score 0
    1
    1
        After 3 Month induction therapy: Score 1
    8
    4
        After 3 Month induction therapy: Score 2
    11
    0
        After 3 Month induction therapy: Score 3
    8
    2
        After 3 Month induction therapy: Score 4
    7
    2
        After 3 Month induction therapy: Score 5
    4
    2
        After 3 Month induction therapy: Score 6
    3
    1
        After 3 Month induction therapy: Score 7
    2
    1
        After 3 Month induction therapy: Score 8
    1
    0
        After 3 Month induction therapy: Score 9
    1
    0
        After 3 Month induction therapy: missing
    11
    1
        After 1 year SCT or Cont. Ruxo.: Score 0
    7
    0
        After 1 year SCT or Cont. Ruxo.: Score 1
    9
    2
        After 1 year SCT or Cont. Ruxo.: Score 2
    6
    2
        After 1 year SCT or Cont. Ruxo.: Score 3
    6
    1
        After 1 year SCT or Cont. Ruxo.: Score 4
    4
    0
        After 1 year SCT or Cont. Ruxo.: Score 5
    1
    0
        After 1 year SCT or Cont. Ruxo.: Score 6
    1
    0
        After 1 year SCT or Cont. Ruxo.: Score 7
    0
    1
        After 1 year SCT or Cont. Ruxo.: Score 8
    2
    0
        After 1 year SCT or Cont. Ruxo.: Score 9
    1
    0
        After 1 year SCT or Cont. Ruxo.: missing
    20
    8
        After 3 years SCT or Cont. Ruxo.: Score 0
    6
    0
        After 3 years SCT or Cont. Ruxo.: Score 1
    11
    0
        After 3 years SCT or Cont. Ruxo.: Score 2
    2
    1
        After 3 years SCT or Cont. Ruxo.: Score 3
    2
    1
        After 3 years SCT or Cont. Ruxo.: missing
    36
    12
    Attachments
    		 Evaluation of QoL
    No statistical analyses for this end point

    Secondary: Evaluation of QoL (FACT-BMT) and 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

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    End point title
    		 Evaluation of QoL (FACT-BMT) and 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
    End point description
    The Quality of Life Score Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) Score before Ruxolitinib induction therapy (= baseline), after 3 months of Ruxolitinib induction therapy at transplantation at 6 months 1 year 2 years and 3 years were evaluated with frequency tables for the study arm “SCT by visit. Population: FAP_SCT
    End point type
    Secondary
    End point timeframe
    after confinement at 6 months, 1 year, 2 years and 3 years
    End point values
    		 Treatment A: Allogeneic SCT Treatment B: Ruxolitinib continuous therapy
    Number of subjects analysed
    57 [11]
    14 [12]
    Units: patients
        arithmetic mean (standard deviation)
    0 ( 0 )
    0 ( 0 )
    Notes
    [11] - Analysis not conducted
    [12] - Analysis not conducted
    No statistical analyses for this end point

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    Beside the defined expections of AEs all AE within the study period will be recorded in the eCRF. SAE reporting timeframe for this study begins after consenting to study participation until 28 days after SCT or 3 cycles of Ruxolitinib continuous therapy.
    Adverse event reporting additional description
    After SCT the following events are not considered as AE and are therefore not recorded in the eCRF, but a detailed documentation in the patient’s record (source data) is mandatory: • Cytopenia until day +100 post transplantation • Nausea, alopecia, vomiting, or constipation until day +100 post transplantation • CTCAE grade 1 and 2 [...]
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Continuous Ruxolitinib
    Reporting group description
    		 Comparator arm. Safety Population (SP)

    Reporting group title
    Allogeneic SCT Arm
    Reporting group description
    		 Test arm. Safety Population (SP)

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Only SAE are presented.
    Serious adverse events
    		 Continuous Ruxolitinib Allogeneic SCT Arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 16 (31.25%)
    32 / 64 (50.00%)
         number of deaths (all causes)
    2
    9
         number of deaths resulting from adverse events
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myelofibrosis
         subjects affected / exposed
    2 / 16 (12.50%)
    4 / 64 (6.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Orthostatic hypertension
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Disease progression
         subjects affected / exposed
    3 / 16 (18.75%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Chronic graft versus host disease
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Organising pneumonia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    General physical condition abnormal
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Graft complication
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Spinal fracture
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis cytomegalovirus
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye infection
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sepsis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Staphylococcal infection
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxoplasmosis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tuberculosis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Continuous Ruxolitinib Allogeneic SCT Arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 64 (0.00%)

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Aug 2017
    Due to official instructions the protocol version 3.0 was revised: - Restriction due to the origination of the allo-HSC donor. - In the course of the above mentioned changes inconsistencies have been removed and editorial changes have been made.
    25 Mar 2020
    Due to Amendment the protocol version 4.0 was revised: - Recruitment period was prolonged - Inclusion Criteria No. 5 was changed - Insurance company change was adapted

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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