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

Sponsor
Universitätsklinikum Hamburg-Eppendorf (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03333187
Collaborator
Novartis (Industry), Clinical Trial Center North (CTC North GmbH & Co. KG) (Other)
87
Enrollment
14
Locations
2
Arms
105.3
Anticipated Duration (Months)
6.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Allogeneic stem cell transplantation
  • Drug: Ruxolitinib continuous therapy
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
87 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
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 therapyTreatment A (only with a suitable stem cell donor):Allogeneic SCT after 3 months of Ruxolitinib induction therapyTreatment B:Ruxolitinib continuous therapy
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Ruxolitinib Versus Allogeneic Stem Cell Transplantation for Patients With Myelofibrosis According to Donor Availability: A Prospective Phase II Trial (MMM 02 Study)
Actual Study Start Date :
Dec 21, 2016
Anticipated Primary Completion Date :
Oct 1, 2024
Anticipated Study Completion Date :
Oct 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

Treatment with Allogeneic Stem cell Transplantation after 3 months of Ruxolitinib induction therapy

Procedure: Allogeneic stem cell transplantation
Active Comparator: Arm B

Treatment with Ruxolitinib continuous therapy

Drug: Ruxolitinib continuous therapy
Other Names:
  • Jakavi

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Spleen reduction [3 months]

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

    2. 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

    3. Improvement of bone marrow fibrosis [3 months]

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

    4. 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

    5. 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

    6. Toxicity of Ruxolitinib [till 3 years]

      Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0

    7. Toxicity of conditioning therapy [till 3 years]

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

    8. Relapse [3 years]

      Cumulative incidence of relapse at 3 years after allogeneic SCT

    9. Disease-related mortality [3 years]

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

    10. Non-relapsed mortality [1 and 3 years]

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

    11. Discontinuation rate [3 years]

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

    12. Evaluation of Sorror Risk Score [at baseline]

      Evaluation of Sorror Risk Score on outcome after allogeneic SCT

    13. 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

    14. 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

    15. 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

    16. 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

    17. 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

    18. 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

    19. 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

    20. Overall Survival [3 years]

      Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suit-able donor

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    1. Positive serology for HIV

    2. Pregnant or lactating women (positive serum pregnancy test)

    3. Age < 18 and ≥ 71 years.

    4. Uncontrolled invasive fungal infection at time of screening (baseline)

    5. Serious psychiatric or psychological disorders

    6. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment

    7. Transformation to AML

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Universitätsklinkum Aachen Aachen Germany 52074
    2 HELIOS Klinikum Berlin-Buch Berlin Germany 13125
    3 Universitätsklinikum Bonn Bonn Germany 53105
    4 Universitätsklinikum Düsseldorf Düsseldorf Germany 40225
    5 Universitätsklinkum Halle Halle (Saale) Germany 06120
    6 University Medical Center Hamburg-Eppendorf Hamburg Germany 20246
    7 Universitätsklinikum Jena Jena Germany 07747
    8 Universitätsmedizin der Johannes Gutenberg-Universität Mainz Mainz Germany 55131
    9 Johannes Wesling Klinikum Minden Minden Germany 32429
    10 Universitätsklinikum Münster Munster Germany 48149
    11 Klinikum Nürnberg Nürnberg Germany 90419
    12 Robert-Bosch-Krankenhaus Stuttgart Stuttgart Germany 70376
    13 Universitätsmedizin Tübingen Tübingen Germany 72076
    14 Universitätsklinkum Ulm Ulm Germany 89081

    Sponsors and Collaborators

    • Universitätsklinikum Hamburg-Eppendorf
    • Novartis
    • Clinical Trial Center North (CTC North GmbH & Co. KG)

    Investigators

    • Principal Investigator: Nicolaus Kröger, Prof. Dr., Universitätsklinikum Hamburg-Eppendorf

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Universitätsklinikum Hamburg-Eppendorf
    ClinicalTrials.gov Identifier:
    NCT03333187
    Other Study ID Numbers:
    • MMM 02 study / RuxoAlloStudy
    First Posted:
    Nov 6, 2017
    Last Update Posted:
    Aug 23, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Universitätsklinikum Hamburg-Eppendorf
    Myelofibrosis, Myeloproliferative Disease
    Additional relevant MeSH terms:
    Primary Myelofibrosis

    Study Results

    No Results Posted as of Aug 23, 2021