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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03333187
Recruitment Status : Active, not recruiting
First Posted : November 6, 2017
Last Update Posted : August 23, 2021
Sponsor:
Collaborators:
Novartis
Clinical Trial Center North (CTC North GmbH & Co. KG)
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf

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
Bone Marrow Fibrosis 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.

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Study Type : Interventional  (Clinical Trial)
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 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 : December 21, 2016
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2025


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 Name: Jakavi




Primary Outcome Measures :
  1. Event free survival [ Time Frame: 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 [ Time Frame: 3 months ]
    Ultrasound measurement Spleen size, reduction of Spleen size after 3 months Ruxolitinib induction therapy

  2. Improvement of constitutional symptoms [ Time Frame: 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 [ Time Frame: 3 months ]
    bone marrow histology, Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy

  4. Acute graft-versus-host disease [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: till 3 years ]
    Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0

  7. Toxicity of conditioning therapy [ Time Frame: till 3 years ]
    Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0

  8. Relapse [ Time Frame: 3 years ]
    Cumulative incidence of relapse at 3 years after allogeneic SCT

  9. Disease-related mortality [ Time Frame: 3 years ]
    Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous therapies

  10. Non-relapsed mortality [ Time Frame: 1 and 3 years ]
    Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy

  11. Discontinuation rate [ Time Frame: 3 years ]
    Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study)

  12. Evaluation of Sorror Risk Score [ Time Frame: at baseline ]
    Evaluation of Sorror Risk Score on outcome after allogeneic SCT

  13. Chimerism on relapse [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 3 years ]
    Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suit-able donor



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03333187


Locations
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Germany
Universitätsklinkum Aachen
Aachen, Germany, 52074
HELIOS Klinikum Berlin-Buch
Berlin, Germany, 13125
Universitätsklinikum Bonn
Bonn, Germany, 53105
Universitätsklinikum Düsseldorf
Düsseldorf, Germany, 40225
Universitätsklinkum Halle
Halle (Saale), Germany, 06120
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitätsklinikum Jena
Jena, Germany, 07747
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Germany, 55131
Johannes Wesling Klinikum Minden
Minden, Germany, 32429
Universitätsklinikum Münster
Munster, Germany, 48149
Klinikum Nürnberg
Nürnberg, Germany, 90419
Robert-Bosch-Krankenhaus Stuttgart
Stuttgart, Germany, 70376
Universitätsmedizin Tübingen
Tübingen, Germany, 72076
Universitätsklinkum Ulm
Ulm, Germany, 89081
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Novartis
Clinical Trial Center North (CTC North GmbH & Co. KG)
Investigators
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Principal Investigator: Nicolaus Kröger, Prof. Dr. Universitätsklinikum Hamburg-Eppendorf
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Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT03333187    
Other Study ID Numbers: MMM 02 study / RuxoAlloStudy
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: August 23, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases