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VALIDATION OF A PREDICTIVE MODEL OF RESPONSE TO ROMIPLOSTIM IN PATIENTS WITH IPSS LOW OR INTERMEDIATE-1 RISK MDS AND THROMBOCYTOPENIA (EUROPE)

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ClinicalTrials.gov Identifier: NCT02335268
Recruitment Status : Recruiting
First Posted : January 9, 2015
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: N-Plate / romiplostim Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 1, 2015
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Romiplostim

Arm Intervention/treatment
Experimental: Group 1

Stratification 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

Drug: N-Plate / romiplostim
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

Experimental: Group 2

Stratification 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

Drug: N-Plate / romiplostim
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

Experimental: Group 3

Stratification 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

Drug: N-Plate / romiplostim
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




Primary Outcome Measures :
  1. Hematologic improvement of platelets (HI-P) after 4 months on therapy [ Time Frame: up to 12 months ]

Secondary Outcome Measures :
  1. Cumulative hematologic improvement of platelets (HI-P), erythrocytes (HI-E) and neutrophils (HI-N) [ Time Frame: up to 12 months ]
  2. The incidence of disease progression to higher stage MDS or AML [ Time Frame: up to 12 months ]
  3. Increase of peripheral blasts during therapy [ Time Frame: up to 12 months ]
  4. Association of the presence of certain mutations with disease progression in a retrospective analysis [ Time Frame: up to 12 months ]
  5. Incidence of bleeding events [ Time Frame: up to 12 months ]
  6. 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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02335268


Contacts
Contact: Katja Reichardt, Dr. 0049 351 25933 ext 188 katja.reichardt@gwtonline.de

Locations
Germany
MVZ Onkologischer Schwerpunkt am Oskar-Helene-Heim Active, not recruiting
Berlin, Germany
Vivantes Klinikum am Urban / Hämatologie Onkologie Active, not recruiting
Berlin, Germany
Klinikum Chemnitz gGmbH / Klinik für Innere Medizin III Recruiting
Chemnitz, Germany, 09116
Contact: Mathias Hänel, PD         
Universitätsklinikum Dresden / Medizinische Klinik I Recruiting
Dresden, Germany, 01307
Contact: Uwe Platzbecker, Prof.         
Marienhospital Düsseldorf GmbH / Innere Medizin u. Hämatologie Recruiting
Düsseldorf, Germany
Contact: Aristoteles Giagounidis, PD         
Universitätsklinikum Halle (Saale) / Klinik für Innere Medizin IV Recruiting
Halle, Germany, 06120
Contact: Haifa Kathrin Al-Ali, PD         
Universitätsklinikum Hamburg-Eppendorf /Onkologisches Zentrum Active, not recruiting
Hamburg, Germany, 20246
Asklepios Kliniken St. Georg / Hämatologie, Onkologie Withdrawn
Hamburg, Germany
Medizinische Hochschule Hannover / Hämatologie u. Onkologie Recruiting
Hannover, Germany
Contact: Michael Heuser, PD         
Universitätsklinikum Mannheim / Klinik III / Hämatologie, Onkologie Recruiting
Mannheim, Germany
Contact: Georgia Metzgeroth, Prof.         
Gemeinschaftspraxis Hämatologie/Onkologie Withdrawn
München, Germany
Klinikum Rechts der Isar, Tumortherapiezentrum Recruiting
München, Germany
Contact: Katharina Götze, PD         
MVZ für Blut u. Krebserkrankungen Active, not recruiting
Potsdam, Germany
Universitätsklinikum Ulm / Klinik Innere Medizin III Recruiting
Ulm, Germany
Contact: Richard Schlenk, Prof.         
Onkologische Gemeinschaftspraxis Active, not recruiting
Weilheim, Germany
Rems-Murr-Kliniken Winnenden / Hämatologie, Onkologie Recruiting
Winnenden, Germany
Contact: Stefani Parmentier, Dr.         
Sponsors and Collaborators
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
Investigators
Study Director: Uwe Platzbecker, Prof. Dr. University of Dresden
Study Director: Lionel Ades, Prof. Dr. Groupe Francophone des Myelodysplasies

Responsible Party: Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinicalTrials.gov Identifier: NCT02335268     History of Changes
Other Study ID Numbers: 440/47 EUROPE
First Posted: January 9, 2015    Key Record Dates
Last Update Posted: May 10, 2017
Last Verified: May 2017

Keywords provided by Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH:
MDS classified as IPSS low/int-1

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Thrombocytopenia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Blood Platelet Disorders