Clinical trial NCT03333187: Ruxolitinib vs Allogeneic SCT for Patients With Myelofibrosis According to Donor Availability
Official title: Ruxolitinib Versus Allogeneic Stem Cell Transplantation for Patients With Myelofibrosis According to Donor Availability: A Prospective Phase II Trial (MMM 02 Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Bone Marrow Fibrosis
Keywords: Myelofibrosis, Myeloproliferative Disease
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Novartis
name: Clinical Trial Center North (CTC North GmbH & Co. KG)
First posted: 2017-11-06
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Event free survival
timeFrame: 3 years
Secondary outcomes:
measure: Spleen reduction
timeFrame: 3 months
measure: Improvement of constitutional symptoms
timeFrame: 3 months
measure: Improvement of bone marrow fibrosis
timeFrame: 3 months
measure: Acute graft-versus-host disease
timeFrame: Day +100 after allogeneic SCT
measure: Chronic graft-versus-host disease
timeFrame: 1, 2 and 3 years after allogeneic SCT
measure: Toxicity of Ruxolitinib
timeFrame: till 3 years
measure: Toxicity of conditioning therapy
timeFrame: till 3 years
measure: Relapse
timeFrame: 3 years
measure: Disease-related mortality
timeFrame: 3 years
measure: Non-relapsed mortality
timeFrame: 1 and 3 years
measure: Discontinuation rate
timeFrame: 3 years
measure: Evaluation of Sorror Risk Score
timeFrame: at baseline
measure: Chimerism on relapse
timeFrame: 30d, 100d, 180 d, 1 year, 2 years and 3 years
measure: Bone marrow fibrosis regression
timeFrame: 30d, 100d, 1 year, and 3 years
measure: Bone marrow fibrosis regression
timeFrame: 30d, 100d, 1 year and 3 years
measure: Evaluation of QOL (FACT-BMT)
timeFrame: baseline, at transplantation, +180d, +1 year, +2 years and +3 years
measure: Evaluation of QOL (MPN-SAF-TSS)
timeFrame: baseline, at transplantation, +180d, +1 year, +2 years and +3 years
measure: Evaluation of QOL (FACT-BMT)
timeFrame: baseline, confinement to Ruxolitinib continous therapy, +180d, +1 year, +2 years and +3 years
measure: Evaluation of QOL (MPN-SAF-TSS)
timeFrame: baseline, confinement to Ruxolitinib continous therapy, +180d, +1 year, +2 years and +3 years
measure: Overall Survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Universitätsklinkum Aachen
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Halle (Saale)
country: Germany
facility: Universitätsklinkum Halle
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: Munster
country: Germany
facility: Universitätsklinikum Münster
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus Stuttgart
city: Tübingen
country: Germany
facility: Universitätsmedizin Tübingen
city: Ulm
country: Germany
facility: Universitätsklinkum Ulm
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Nicolaus Kröger, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: