Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00010750

Trial Description

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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

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Trial Acronym

EUROPE

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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.

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Organizational Data

  •   DRKS00010750
  •   2016/06/29
  •   2015/01/07
  •   yes
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Secondary IDs

  •   NCT02335268  (ClinicalTrials.gov)
  •   440/47 EUROPE  (Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH)
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Health Condition or Problem studied

  •   Myelodysplastic Syndromes
  •   D46 -  Myelodysplastic syndromes
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Interventions/Observational Groups

  •   Drug: N-Plate / romiplostim
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Characteristics

  •   Interventional
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  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

- Hematologic improvement of platelets (HI-P) after 4 months on therapy; time frame: up to 12 months

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Secondary Outcome

- Cumulative hematologic improvement of platelets (HI-P), erythrocytes (HI-E) and neutrophils (HI-N); time frame: up to 12 months
- The incidence of disease progression to higher stage MDS or AML; time frame: up to 12 months
- Increase of peripheral blasts during therapy; time frame: up to 12 months
- Association of the presence of certain mutations with disease progression in a retrospective analysis; time frame: up to 12 months
- Incidence of bleeding events; time frame: up to 12 months
- Type, incidence and severity of all adverse events including clinically significant changes in laboratory values; time frame: up to 12 months

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2015/06/30
  •   90
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- 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

- 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.

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Exclusion Criteria

- 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

- 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.

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Addresses

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    • Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
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    • University of Dresden
    • Uwe Platzbecker, Prof. Dr. 
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    • Katja Reichardt, Dr. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2016/06/22
* This entry means the parameter is not applicable or has not been set.