HOVON 89

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.