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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Bone Marrow Fibrosis
• Intervention / Treatment: Procedure: Allogeneic stem cell transplantation; Drug: Ruxolitinib continuous therapy

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 Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Universitätsklinkum Aachen
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
  • Halle (Saale), Germany, 06120
    • Universitätsklinkum Halle
  • Hamburg, Germany, 20246
    • University Medical Center Hamburg-Eppendorf
  • Jena, Germany, 07747
    • Universitätsklinikum Jena
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Minden, Germany, 32429
    • Johannes Wesling Klinikum Minden
  • Munster, Germany, 48149
    • Universitatsklinikum Munster
  • Nürnberg, Germany, 90419
    • Klinikum Nürnberg
  • Stuttgart, Germany, 70376
    • Robert-Bosch-Krankenhaus Stuttgart
  • Tübingen, Germany, 72076
    • Universitätsmedizin Tübingen
  • Ulm, Germany, 89081
    • Universitätsklinkum Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2016
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Myelofibrosis, Myeloproliferative Disease
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: MMM 02 study / RuxoAlloStudy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No