Main info

Identificatie:

HOVON 89 MDS

Sponsor:

HOVON

Working group party:

Leukemia

Age:

>= 18

Stadium:

1st lijn

Echelon:

Level D

Included patients:

200

(of 200)

Active sites:

60

(of 46)

Title:

A Phase II randomized multicenter study to assess the efficacy of lenalidomide with or without erythropoietin and granulocyte-colony stimulating factor in patients with low and intermediate-1 risk myelodysplastic syndrome.

Timeline

Flow

Details

Phase:

Prospective Phase II study

Monitoring Type:

Not any more

Objectives:

Primary objective

• To evaluate the efficacy of lenalidomide (RevlimidTM) in low/int-1 risk MDS with or without a treatment with Epo (NeoRecormonTM)/G-CSF (NeupogenTM) in terms of hematological improvement (HI) as defined by the modified response criteria of the IWG for MDS [40], see appendix C.

Secondary objectives

• To evaluate the safety and tolerability of lenalidomide (RevlimidTM) in low/int-1 risk MDS with or without Epo (NeoRecormonTM)/G-CSF (NeupogenTM)
• Time-to-HI and duration-of-HI
• The number of given treatment cycles per patient and for arm B the number of patients receiving Epo and/or G-CSF
• The response rate (in terms of CR, PR, including cytogenetic response according to the modified response criteria of the IWG for MDS [40], see appendix C)
• Progression-Free-Survival (i.e. time from registration to disease progression, including progression to leukemia, or death from any cause)
• Transfusion requirements of red blood cells

Eligibility

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 ≤ 12x10^9/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 ≤ 1.0x10^9/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 billirubin < 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.

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, autoimmune 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) < 0.5x10^9/l
• Patients dependent on platelet transfusions or with platelet counts < 25x10^9/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

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals