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

Bone Marrow Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03333187
• Other study ID #: MMM 02 study / RuxoAlloStudy
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 21, 2016
• Est. completion date: October 2025

Study information

• Verified date: August 2021
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 87
• Est. completion date: October 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Bone Marrow Fibrosis
• Primary Myelofibrosis

Intervention

Procedure:
• Allogeneic stem cell transplantation

Drug:
• Ruxolitinib continuous therapy

Locations

Country	Name	City	State
Germany	Universitätsklinkum Aachen	Aachen
Germany	HELIOS Klinikum Berlin-Buch	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitätsklinkum Halle	Halle (Saale)
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	Munster
Germany	Klinikum Nürnberg	Nürnberg
Germany	Robert-Bosch-Krankenhaus Stuttgart	Stuttgart
Germany	Universitätsmedizin Tübingen	Tübingen
Germany	Universitätsklinkum Ulm	Ulm

Sponsors (3)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Clinical Trial Center North (CTC North GmbH & Co. KG), Novartis

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Spleen reduction	Ultrasound measurement Spleen size, reduction of Spleen size after 3 months Ruxolitinib induction therapy	3 months
Secondary	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
Secondary	Improvement of bone marrow fibrosis	bone marrow histology, Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy	3 months
Secondary	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
Secondary	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
Secondary	Toxicity of Ruxolitinib	Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0	till 3 years
Secondary	Toxicity of conditioning therapy	Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0	till 3 years
Secondary	Relapse	Cumulative incidence of relapse at 3 years after allogeneic SCT	3 years
Secondary	Disease-related mortality	Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous therapies	3 years
Secondary	Non-relapsed mortality	Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy	1 and 3 years
Secondary	Discontinuation rate	Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study)	3 years
Secondary	Evaluation of Sorror Risk Score	Evaluation of Sorror Risk Score on outcome after allogeneic SCT	at baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Survival	Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suit-able donor	3 years