Originele protocol

Inclusion criteria

  • Patients with MDS classified as
    • RA, RARS and RAEB (with <10% myeloid blasts), CMML (with <10% myeloid blasts), according to FAB (see appendix A3) or
    • RA, RARS, RCMD, RCMD-RS, RAEB-1, MDS-U according to WHO (see appendix A1) or
    • patients with MPD/MDS (CMML-1 according to WHO) with a WBC ≤ 12×109/l (see appendix A2) with an IPSS ≤ 1.0 (see appendix B1).
  • Hb ≤ 6.2 mmol/l (10.0 g/dl)
    or Hb ≤ 7.2 mmol/l and ANC ≤ 1.0×109/l
    or red blood cell transfusion dependent (≥ 2 units RBC during at least 8 weeks; units must be given for a Hb ≤ 5.6 mmol/l).
  • Age ≥ 18 years- WHO performance status 0-2 (see appendix D).
  • Patient not previously treated with Epo/G-CSF, or failure of response or relapse after hematological improvement or disease progression to maximal RAEB-1 after previous therapy with Epo/G-CSF.
  • Serum creatinin < 150 µmol/l.
  • Serum bilirubin < 25 µmol/l and ASAT, ALAT and Alkaline phosphatase < 2.5 times the upper limit of normal, except if related to disease.
  • The patient must give written informed consent.
  • Negative pregnancy test within 7 days prior to start of study drug, if applicable.
  • Patient (all men, pre-menopausal women) agrees to use adequate contraceptive methods.
  • Serum erythropoietin level
    > 200 U/l or
    ≤ 200 U/l if failure of response or loss of hematological improvement or disease progression to maximal RAEB-1 after prior standard therapy with Epo/G-CSF; Epo/G-CSF should be stopped at least 1 month before randomization. Note: any cytogenetic karyotype can be included (normal and abnormal (including del(5q) abnormalities).

Exclusion criteria

  • Severe cardiac, pulmonary, neurologic, metabolic or psychiatric diseases or active malignancies.
  • Anemia due to other causes than MDS including iron, B12 and folate deficiencies, auto-immune hemolysis and/or paroxysmal noctural hemoglobinuria (PNH).
  • Hypoplastic MDS.
  • High predictive score (score 0 or 1) to respond on standard treatment with Epo/G-CSF according to guidelines; see appendix H.
  • Active uncontrolled infection.
  • Absolute neutrophil count (ANC) < 0.5×109/l.
  • Patients dependent on platelet transfusions or with platelet counts < 25×109/l or patients with active bleeding.
  • Patients treated with biological response modifiers (i.e. growth factors, immunosuppressive agents and/or chemotherapy) within 1 month prior to randomization.
  • Lactating women.
  • Prior treatment with lenalidomide.
  • Prior CTCAE ≥ grade 3 allergic reaction/hypersensitivity to thalidomide.
  • Prior CTCAE ≥ grade 3 rash/blistering while taking thalidomide.
  • Prior CTCAE ≥ grade 3 allergic/hypersensitivity to Epo and/or G-CSF.