AzTrials
AzTrials

Graft vs Host DiseasePhase 2RIGNCT02396628

Ruxolitinib In GvHD

A Phase 2 study testing Experimental intervention and Standard treatment in people with Graft vs Host Disease, run by Prof. Dr. Nikolas von Bubnoff at 11 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The preliminary data demonstrate potent activity of Ruxolitinib in steroid-refractory aGvHD. In this phase 2 trial the efficacy of Ruxolitinib and best available treatment (BAT) versus BAT in steroid-refractory acute GvHD in approximately 12 transplantation centers in Germany will be compared. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft vs Host Disease
What is being tested?
Experimental intervention and Standard treatment
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
11 sitesGermany
Study dates
29 Jun 2017to 15 Nov 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Acute skin, intestinal (histologically confirmed) or liver GvHD > grade 1 according to standard criteria
  • Age ≥18 years
  • Failure of previous treatment, defined as presence of at least one of the following criteria:
  • Treatment with prednisone/prednisolone/methylprednisolone in a dose of at least 2 mg/kg and lack of response after at least 7 days treatment
  • Treatment with prednisone/prednisolone/methylprednisolone in a dose of at least 2 mg/kg and progression after at least 3 days of treatment
  • Failure to taper the prednisone/prednisolone dose to <0.6 mg/kg/day or methylprednisolone dose to <0.5 mg/kg/day
  • Written informed consent
  • Ability to understand the nature of the study and the study related procedures and to comply with them

Who cannot join

  • Uncontrolled underlying disease
  • Active bleeding
  • Absence of clinical signs of acute GvHD
  • Diagnostic or distinctive clinical signs of chronic GvHD
  • Uncontrolled bacterial, viral or fungal infection
  • Absolute neutrophil count <0.5x103/µl
Show all 12Show fewer
  • Evidence of transplant-associated micrioangiopathy (TAM) (According to Jodele et al., 2015, diagnostic criteria for TAM)
  • Any previous JAK2 inhibitor treatment prior to study enrolment, except Ruxolitinib given prior to the allogeneic stem cell transplantation
  • Known Hypersensitivity to Ruxolitinib or any of the excipients
  • Known positivity for HIV, Hepatitis B or Hepatitis C at the time of screening.
  • Female patients who are pregnant or breast feeding
  • Concomitant use of any other investigational drug within the last thirty days before the start of this study

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Germany11 sites

  • Charité - Universitätsmedizin Berlin

    Berlin, 13353

  • Universitätsklinikum Bonn

    Bonn, 53105

  • Universitätsklinikum Köln

    Cologne, 50937

  • Universitätsklinikum Dresden

    Dresden, 01307

  • University Medical Center

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

  • Universitätsklinikum Marburg

    Marburg, 35043

  • Universitätsklinikum München TU rechts der Isar

    München, 81675

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

About this study

Official title: Multicentre Phase 2 Trial to Evaluate the Efficacy of Ruxolitinib in Steroid-refractory Acute Multicenter, Randomized Phase 2 Trial to Determine the Response Rate of Ruxolitinib and Best Available Treatment (BAT) Versus BAT in Steroid-refractory Acute Graft-versus-Host Disease (aGvHD)

The preliminary data demonstrate potent activity of Ruxolitinib in steroid-refractory aGvHD. In this phase 2 trial the efficacy of Ruxolitinib and best available treatment (BAT) versus BAT in steroid-refractory acute GvHD in approximately 12 transplantation centers in Germany will be compared. The response by monitoring the clinical GvHD grade, requirement of alternative GvHD active agents and serum levels of pro-inflammatory cytokines will be determined.

Read the detailed description

The pathophysiological hallmark of GvHD after allo-HCT is an allogeneic donor T cell re-sponse against recipient antigens. This process is aggravated by increased processing and presentation of host antigens by donor APCs following conditioning treatment. The al-logeneic T cell response leads to inflammation, tissue damage and fibrosis and is mediated by extensive production of inflammatory cytokines such as IL-1, IL-2R, IL-6 and TNF. The signal transmission of inflammatory cytokines in effector cells requires activation of specialized kinases from the family of the Janus kinases. These kinases, JAK1, 2 and 3 are linked to cytokine receptors, and are activated upon binding of the cytokine to the receptor of the inflammatory effector. The JAK1/2 kinase inhibitor Ruxolitinib (INC424) is approved for myelofibrosis. In advanced myelofibrosis, Ruxolitinib lead to sustained clinical remissions with regard to constitutional symptoms, weight loss and spleen size in the majority of treated patients. Of note, clinical responses correlated with a marked reduction in inflammatory plasma cytokines.

Importantly, cytokines down-regulated by Ruxolitinib in patients with myelofibrosis correspond to inflammatory effectors that mediate tissue damage and inflammation in GvHD. These are mainly the cytokines IL- 1, IL -6, TNF and IFN-gamma. Since Ruxolitinib suppresses the JAK1 / 2 cytokine response, we hypothesized that Ruxolitinib might attenuate the cytokine mediated inflammatory tissue damage in GVHD and thus might favourably affect the severity and course of GvHD after allo-HCT.

In vitro, we demonstrated in an allogeneic system (major mismatch mixed-lymphocyte reactions) that co-incubation with Ruxolitinib strongly suppressed both the proliferation of alloge-neic T cells and the production of inflammatory cytokines. Using a very aggressive major mismatch mouse model of acute GvHD Ruxolitinib treatment signifi-cantly prolonged survival of animals (see Figure 1A). In addition, in these animals showed a reduced weight loss, significantly reduced histopathological GvHD severity, suppression of inflammatory cytokines in the serum and a reduction of donor T cells in GvHD target organs such as the intestines.

Sole suppression of cytokine production or cytokine receptor activity by Ruxolitinib would be very similar to already established drugs for GvHD and no major conceptual advance. However we observed that Ruxolitinib did not only suppress cytokine production but also led to increased frequencies of FoxP3+ regulatory T cells. This cell type was previ-ously shown to lead to long-lasting tolerance as compared to the short-term immunosuppression achieved by conventional medication for GvHD.

Being tested
Experimental intervention, Standard treatment
Keywords
Graft-versus-Host Disease (GvHD), resistance to therapy, allogeneic stem cell transplantation, Ruxolitinib
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Experimental interventionDrug

    Treatment with Ruxolitinib at a dose of 10 mg BID orally addition to BAT according DGHO-Onkopedia guidelines

  • Standard treatmentDrug

    Treatment according to DGHO-Onkopedia guidelines for treatment of acute GvHD (as of March 2018). Optional cross over from BAT to Ruxolitinib and BAT in case of lack of response from day 28.

Study groups in NCT02396628
Study groupRoleWhat they receive
Experimental interventionExperimentalTreatment with Ruxolitinib at a dose of 10 mg BID orally addition to BAT according DGHO-Onkopedia guidelines.
Receives: Drug: Experimental intervention
Standard treatmentActive comparatorTreatment according to DGHO-Onkopedia guidelines for treatment of acute GvHD (as of March 2018). Optional cross over from BAT to Ruxolitinib and BAT in case of lack of response from day 28.
Receives: Drug: Standard treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. efficacy of Ruxolitinib and BAT as compared to BAT alone at day 28 after randomisation

    To evaluate efficacy of Ruxolitinib and BAT as compared to BAT alone at day 28 after randomisation start in steroid-refractory acute GvHD, measured as response rate

    Measured: at day 28 after randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2015 (estimated)
  2. Study start29 Jun 2017
  3. Primary completion15 Nov 2019
  4. Study completion15 Nov 2019

Why it stopped: impossibility to recruit in the BAT arm

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02396628
Sponsor's protocol ID
RIG-P000814
Other IDs
2014-004267-20, DRKS00007939, 2014
Acronym
RIG
Status last verified
Nov 2019
First submitted
10 Mar 2015
Last updated
2 Dec 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • von Bubnoff N, Ihorst G, Grishina O, Rothling N, Bertz H, Duyster J, Finke J, Zeiser R. Ruxolitinib in GvHD (RIG) study: a multicenter, randomized phase 2 trial to determine the response rate of Ruxolitinib and best available treatment (BAT) versus BAT in steroid-refractory acute graft-versus-host disease (aGvHD) (NCT02396628). BMC Cancer. 2018 Nov 19;18(1):1132. doi: 10.1186/s12885-018-5045-7.

    PubMed 30453910

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Experimental intervention and Standard treatment in people with Graft vs Host Disease, run by Prof. Dr. Nikolas von Bubnoff at 11 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: impossibility to recruit in the BAT arm). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

efficacy of Ruxolitinib and BAT as compared to BAT alone at day 28 after randomisation (time frame: at day 28 after randomisation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02396628, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in