Clinical trial NCT02928419 (phase 2, status: terminated)
Conditions: myelodysplastic syndromes
ICD codes: D46.9, D46.C, D46.Z
Drugs: eltrombopag/revolade, lenalidomide
SMILES: CC1=NN(C(=O)\C1=N/NC1=C(O)C(=CC=C1)C1=CC=CC(=C1)C(O)=O)C1=CC=C(C)C(C)=C1, NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O
Reason stopped: 
    "the study has been closed due to a low rate of patient enrollment (2 patients since the start
    of the trial)"
  
Eligibility criteria:

        Inclusion Criteria:

          -  Adult subjects (18 years of age or older) with MDS and low or intermediate-1 IPSS risk
             and del5q as a single abnormality, at the time of their screening and enrollment into
             the study

          -  Subjects must not have received any prior treatment course with any immunomodulating
             agent nor TPO-R agonists

          -  Subjects must be dependent on regular packed RBC transfusions, as defined by
             international working group 2006 criteria, and must have a PLT count taken within the
             4 weeks prior to screening that is >25 Gi/L.

          -  Absolute Neutrophil Counts (ANC) ≥ 0.5 GiL

          -  Resistant or refractory to erythropoetic stimulating agents (ESAs) and/or serum
             erythropoetin levels > 500 miU/L

          -  Subjects must be ineligible or relapsed or refractory to receive treatment options of
             azacitidine and decitabine.

          -  Subjects must have PLT count and RBC and PLT transfusion data available over a period
             of 8 weeks prior to screening.

          -  During the 2 months prior to randomization, subjects must have a baseline BM
             examination including all of the following: cytomorphology, cytogenetics and histology

          -  ECOG Performance Status must be 0-3.

          -  The following clinical chemistries MUST NOT exceed the upper limit of normal (ULN)
             reference range: creatinine, ALT, AST, total bilirubin (except for Gilbert's
             Syndrome), gamma-gt and alkaline phosphatase. In addition, albumin must not be below
             the lower limit of normal (LLN) by more than 10%.

          -  If subject meets the criteria for childbearing potential:

               1. Negative pregnancy test in female subjects within the 3 days prior to Day 1 of
                  1st cycle and effective contraception for at least 4 weeks.

               2. Subject is practicing an acceptable method of contraception (documented in
                  chart). Female subjects (or female partners of male subjects) must either be of
                  non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal
                  ligation or post-menopausal >1 year), or of childbearing potential and use of an
                  highly effective method of contraception from 2 weeks prior to administration of
                  study medication, throughout the study, and 28 days after completion or premature
                  discontinuation from the study.

          -  Criteria for women of non-childbearing potential: A female patient or a female partner
             of a male patient is considered to have childbearing potential unless she meets at
             least one of the following criteria:

               1. Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year (amenorrhoea following
                  cancer therapy or during lactation does not rule out childbearing potential).

               2. Premature ovarian failure confirmed by a gynaecologist

               3. Previous bilateral salpingo-oophorectomy, or hysterectomy

               4. XY genotype, Turner syndrome, uterine agenesis.

          -  Subject is able to understand and comply with protocol requirements and instructions.

          -  Subject has signed and dated informed consent.

        Exclusion Criteria:

          -  MDS with intermediate-2 or high IPSS risk

          -  Additional cytogenetic abnormalities

          -  Transfusion independence (TI) by IWG 2006 criteria

          -  Absolute Neutrophil Count < 0.5 Gi/L and/or Platelet counts < 25 Gi/L

          -  History of treatment for cancer with systemic chemotherapy and/or radiotherapy within
             the last 2 years

          -  History of treatment with immunomodulatory drugs or other TPO-R agonists.

          -  Thrombophilia, pre-existing history of thrombosis, cardiovascular disease (including
             congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or
             arrhythmia known to increase the risk of thromboembolic events (e.g. atrial
             fibrillation), or subjects with a QTc >450 msec (QTc >480 msec for subjects with
             Bundle Branch Block)

          -  Bone Marrow fibrosis that leads to an inability to aspirate marrow for assessment.

          -  Leukocytosis >=25,000/uL prior to Day 1 of study medication.

          -  Monocytosis > 1000/ uL prior to Day 1 of study medication.

          -  Female subjects who are nursing or pregnant (positive serum or urine Beta-human
             chorionic gonadotropin [B-hCG] pregnancy test).

          -  Women of childbearing potential unless all of the conditions of the Pregnancy
             Prevention Programme illustrated in sections 6.4 are met (see sections 6.4).

          -  Known hypersensitivity to lenalidomide.

          -  Current alcohol or drug abuse.

          -  Treatment with an Investigational Product within 30 days or 5 half-lives (whichever is
             longer) preceding the first dose of study medication.

          -  Active and uncontrolled infections.

          -  Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).