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Myelodysplastic SyndromesPhase 2EUROPENCT02335268

Validation of a Predictive Model of Response to Romiplostim in Patients With IPSS Low or Intermediate-1 Risk MDS and Thrombocytopenia

A Phase 2 study testing N-Plate / romiplostim in people with Myelodysplastic Syndromes, run by Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH at 36 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

There are currently no licensed drugs in the EU to treat thrombocytopenia in MDS patients classified as IPSS low/int-1. Prior studies with romiplostim (a TPO receptor agonist) in MDS found that baseline concentration of TPO as well as transfusion history were predictive of subsequent response in a retrospective model. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
N-Plate / romiplostim
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
36 sitesin 2 countries
Study dates
21 May 2015to 1 Jul 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Subjects must meet the following inclusion/exclusion criteria to be eligible for the study.
  • Must understand and voluntarily sign the informed consent form
  • Age older 18 years at the time of signing the informed consent form
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Diagnosis of MDS using the 2008 WHO classification for myeloid neoplasms as assessed during the screening period
  • Per MDS IPSS, low or intermediate-1 risk MDS as assessed during the screening period
Show all 16Show fewer
  • The mean of the 2 platelet counts taken within 4 weeks prior to stratification must be:
  • ≤ 30 x 109/L (with no individual count > 30 x 109/L during the screening period), with or without a history of bleeding associated with the diagnosis of MDS, OR
  • < 50 x 109/L (with no individual count >60 x 109/L during the screening period), with a history of bleeding associated with the diagnosis of MDS (A standard of care platelet count taken prior to Informed consent may be used as 1 of the 2 counts taken within 4 weeks prior to stratification)
  • Adequate liver function, as evidenced by ALT ≤ 3 times the laboratory normal range, AST ≤ 3 times the laboratory normal range and total bilirubin ≤ 2 times the laboratory normal range
  • Bone marrow aspirate (central diagnostics) with cytogenetics (local) within 8 weeks of starting first dose of investigational product
  • Female subjects of childbearing potential† must:
  • Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. Male patients who wish to participate in the study and their partner may become pregnant must agree also to reliable contraception during the study and for three months thereafter.
  • The following are effective methods of contraception
  • Implant, - Levonorgestrel-releasing intrauterine system (IUS), Medroxyprogesterone acetate depot, Tubal sterilization, Sexual intercourse with a vasectomised male partner only; Ovulation inhibitory progesterone-only pills (i.e., desogestrel)
  • Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.

Who cannot join

  • Pregnant or lactating females
  • IPSS intermediate-2 or high-risk
  • ≥ 5% blasts in the bone marrow as determined by central morphology during screening
  • Previous treatment with any thrombopoietic growth factor
  • Prior history of hematopoietic stem cell transplantation, leukemia, aplastic anemia or other non-MDS related bone marrow stem cell disorder
  • Active or uncontrolled disease including infections or cancer
Show all 17Show fewer
  • Unstable angina, congestive heart failure (NYHA > class II), uncontrolled hypertension
  • History of arterial thrombosis (e.g., stroke or transient ischemic attack) within the past year
  • History of venous thrombosis that currently requires anti-coagulation therapy
  • Prior use of sc or iv AZA.
  • Receipt of G-CSF, peg-G-CSF, or GM-CSF,IL-11, ESA or LEN within 4 weeks of the first dose of romiplostim
  • Planned receipt of peg-G-CSF or GM-CSF after the first dose of investigational product
  • Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator. A double barrier method is defined as 2 methods of contraception, for example 2 actual barrier methods, or 1 actual barrier method and 1 hormonal method.
  • Known hypersensitivity to any recombinant E. coli-derived product (eg, Nplate, Infergen, Neupogen, Somatropin, and Actimmune)
  • Inability to comply with study procedures.
  • Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s)
  • Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.

Trial locations and contacts

36 sites in 2 countries.

36 sites in 2 countries

France22 sites

  • CH

    Annecy

  • CH Victor Dupouy

    Argenteuil

  • CH Henri Duffaut

    Avignon

  • CHU de Haut Lévèque

    Bordeaux

  • CHRU Côte de Nacre

    Caen

  • CHU Estaing

    Clermont-Ferrand

  • CHU

    Grenoble

  • CH

    Le Mans

  • CHRU

    Limoges

  • CH Lyon sud

    Lyon

  • IPC

    Marseille

  • CH

    Meaux

  • Clinique Beausoleil

    Montpellier

  • CHU Brabois

    Nancy

  • Centre Catherine de Sienne

    Nantes

  • Polyclinique Le Languedoc

    Narbonne

  • CHR

    Orléans

  • Hôpital Cochin

    Paris

  • Hôpital Saint Louis

    Paris

  • CHU

    Poitiers

  • Centre Henri Becquerel

    Rouen

  • Hôpital Bretonneau

    Tours

Other trials in France

Germany14 sites

  • MVZ Onkologischer Schwerpunkt am Oskar-Helene-Heim

    Berlin

  • Vivantes Klinikum am Urban / Hämatologie Onkologie

    Berlin

  • Klinikum Chemnitz gGmbH / Klinik für Innere Medizin III

    Chemnitz, 09116

  • Universitätsklinikum Dresden / Medizinische Klinik I

    Dresden, 01307

  • Marienhospital Düsseldorf GmbH / Innere Medizin u. Hämatologie

    Düsseldorf

  • Universitätsklinikum Halle (Saale) / Klinik für Innere Medizin IV

    Halle, 06120

  • Universitätsklinikum Hamburg-Eppendorf /Onkologisches Zentrum

    Hamburg, 20246

  • Medizinische Hochschule Hannover / Hämatologie u. Onkologie

    Hanover

  • Universitätsklinikum Mannheim / Klinik III / Hämatologie, Onkologie

    Mannheim

  • Klinikum Rechts der Isar, Tumortherapiezentrum

    München

  • MVZ für Blut u. Krebserkrankungen

    Potsdam

  • Universitätsklinikum Ulm / Klinik Innere Medizin III

    Ulm

  • Onkologische Gemeinschaftspraxis

    Weilheim

  • Rems-Murr-Kliniken Winnenden / Hämatologie, Onkologie

    Winnenden

Other trials in Germany

About this study

Official title: Prospective Validation of a Predictive Model of Response to Romiplostim in Patients With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) and Thrombocytopenia - the EUROPE-trial

There are currently no licensed drugs in the EU to treat thrombocytopenia in MDS patients classified as IPSS low/int-1. Prior studies with romiplostim (a TPO receptor agonist) in MDS found that baseline concentration of TPO as well as transfusion history were predictive of subsequent response in a retrospective model. The current prospective study has the aim to explore whether both pretreatment variables (endogenous TPO, TPO-level, platelet transfusion history) can predict the response to subsequent short-term treatment with romiplostim.

Read the detailed description

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies of the pluripotent hematopoietic stem cells characterized by clonal hematopoiesis, progressive bone marrow failure, and the propensity to transform to acute myeloid leukemia (AML) (Malcovati et al., 2013).

There are currently no licensed drugs in the EU to treat thrombocytopenia in MDS patients classified as IPSS low/int-1. Prior studies with romiplostim (a TPO receptor agonist) in MDS found that baseline concentration of TPO as well as transfusion history were predictive of subsequent response in a retrospective model.

Classically, MDS is associated with apoptosis and excessive proliferation, resulting in a combination of a hyper-cellular marrow and peripheral cytopenia. The rationale for using romiplostim in MDS is to stimulate normal progenitor cells to increase platelet counts. Upon correction of thrombocytopenia, responding MDS patients should have a decreased risk of bleeding and a reduction in platelet transfusions (Giagounidis et al., 2014). This reduction in platelet transfusions may in turn decrease the risks of alloimmunization and the resultant morbidity and costs associated with that condition.

Being tested
N-Plate / romiplostim
Keywords
MDS classified as IPSS low/int-1
Medical subject headings
Myelodysplastic Syndromes

What participants receive

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

  • N-Plate / romiplostimDrug

    medical intervention in 3 patient groups (MDS patients with IPSS Low/Int-1) that are stratified according to their baseline TPO-Level and previous transfusions

Study groups in NCT02335268
Study groupRoleWhat they receive
Group 1ExperimentalStratification into group 1 if Score (Baseline-TPO Level and previous thrombocyte transfusions) are +3 TPO based model to predict subsequent response to romiplostim in MDS patients with IPSS Low/Int-1 according to a model developed by Sekeres et. al./ BJH 2014
Receives: Drug: N-Plate / romiplostim
Group 2ExperimentalStratification into group 2 if Score (Baseline-TPO Level and previous thrombocyte transfusions) are -1 or -2 TPO based model to predict subsequent response to romiplostim in MDS patients with IPSS Low/Int-1 according to a model developed by Sekeres et. al./ BJH 2014
Receives: Drug: N-Plate / romiplostim
Group 3ExperimentalStratification into group 3 if Score (Baseline-TPO Level and previous thrombocyte transfusions) are -6 TPO based model to predict subsequent response to romiplostim in MDS patients with IPSS Low/Int-1 according to a model developed by Sekeres et. al./ BJH 2014
Receives: Drug: N-Plate / romiplostim

What is being measured

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

  1. Hematologic Improvement of Platelets (HI-P) After 4 Months on Therapy

    The primary efficacy endpoint was the rate of HI-P defined as an absolute increase of platelet count to ≥ 30/nL for patients starting at > 20/nL or an increase of platelets from < 20/nL to > 20/nL and by at least 100%, according to IWG 2006 criteria lasting for ≥ 8 weeks after at least 16 Weeks of romiplostim treatment.

    Measured: after 4 months on therapy (week 16)

Secondary outcomes (6)

  1. Cumulative Hematologic Improvement

    Cumulative rate of hematologic improvement of platelets (HI-P), erythrocytes (HI-E) and neutrophil granulocytes (HI-N).

    None of the patients achieved simultaneous response of HI-P, HI-E and HI-N.

    Measured: week 16

  2. The Incidence of Disease Progression to Higher Stage MDS or AML

    The incidence of disease progression to higher stage MDS or AML according to WHO (increase in blast percentage of ≥ 20 %)

    Measured: week 16

  3. Increase of Peripheral Blasts During Therapy

    Measured: week 16

  4. Association of the Presence of Certain Mutations With Disease Progression in a Retrospective Analysis

    Measured: week 16

  5. Incidence of Bleeding Events

    Measured: up to 12 months

  6. Type, Incidence and Severity of All Adverse Events Including Clinically Significant Changes in Laboratory Values

    Measured: up to 12 months

Timeline

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

  1. First posted9 Jan 2015 (estimated)
  2. Study start21 May 2015
  3. Primary completion1 Jul 2021
  4. Study completion1 Jul 2021

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02335268
Sponsor's protocol ID
440/47
Acronym
EUROPE
Status last verified
Jul 2023
First submitted
7 Jan 2015
Last updated
16 Aug 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing N-Plate / romiplostim in people with Myelodysplastic Syndromes, run by Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH at 36 sites in 2 countries.

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 16 inclusion and 17 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: finished, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in France, 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?

Yes. Results are posted in the registry (first posted 14 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Hematologic Improvement of Platelets (HI-P) After 4 Months on Therapy (time frame: after 4 months on therapy (week 16)). 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 NCT02335268.

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 16 Aug 2023.

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