Validation of a Predictive Model of Response to Romiplostim in Patients With IPSS Low or Intermediate-1 Risk MDS and Thrombocytopenia
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Thrombocytopenia; Syndrome
Intervention: N-Plate / romiplostim
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDS classified as IPSS low/int-1

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.
    

Eligibility 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.