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

Phase 2

Completed

Conditions: MDS
myelodysplastic syndrome
10024324

Registration Number: NL-OMON47453

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 200

Inclusion Criteria

- Patients with MDS classified as:
* RA, RARS and RAEB (with <10% myeloid blasts), CMML (with <10% myeloid blasts), according to FAB or
*RA, RARS, RCMD, RCMD-RS, RAEB-1, MDS-U according to WHO or
*patients with MPD/MDS (CMML-1 according to WHO) with a WBC <= 12x109/l with an IPSS <= 1.0
- Hb <= 6.2 mmol/l (10.0 g/dl) or Hb <= 7.2 mmol/l and ANC <= 1.0x109/l or red blood cell transfusion dependent
- Age >= 18 years
- WHO performance status 0-2
- 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, 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
- Active uncontrolled infection
- Absolute neutrophil count (ANC) < 0.5x109/l
- Patients dependent on platelet transfusions or with platelet counts < 25x109/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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint<br /><br>- Hematological improvement (HI) according to IWG 2006 criteria</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints<br /><br>- Adverse events of CTCAE >= grade 2<br /><br>- Time-to-HI and duration-of-HI (i.e. time from HI to relapse after HI or death<br /><br>from any cause)<br /><br>- Number of given treatment cycles per patient, and especially for arm B the<br /><br>number of patients receiving Epo and/or G-CSF<br /><br>- Response rate (in terms of CR, PR, including cytogenetic response according<br /><br>to the modified response criteria of the IWG for MDS<br /><br>- Progression-free-survival, i.e. time from registration to relapse, disease<br /><br>progression or death from any cause<br /><br>- Leukemic evolution. The risk of leukemic evolution will be calculated with<br /><br>competing risk death without previous evolution<br /><br>- Number of transfusions of red blood cells and duration of RBC transfusion<br /><br>independence</p><br>