In a phase I study the investigators plan to investigate safety and toxicity of lenalidomide in patients with Chronic Myelomonocytic Leukemia (CMML). A phase II study will be started once an optimal dose has been found. The primary endpoint will concern the efficacy of lenalidomide in patients with CMML according to the WHO diagnostic criteria.

Inclusion Criteria:

1. CMML according to the WHO diagnostic criteria.

2. Understand and voluntarily sign an informed consent form.

3. Age >=18 years at the time of signing the informed consent form.

4. Able to adhere to the study visit schedule and other protocol requirements.

5. All previous cancer therapy must have been discontinued at least 4 weeks prior to treatment in this study. Patients carrying a somatic mutation involving the platelet derived growth factor receptor beta (PDGFRB) can be included if standard treatment with imatinib failed.

6. ECOG performance status of <= 2 at study entry.

7. Laboratory test results within these ranges:

   • Creatinine clearance > 30ml/min
   • AST (SGOT) and ALT (SGPT) <= 2.5 x ULN

8. Disease free of prior malignancies for >= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

9. Female subjects of childbearing potential must:

   • Understand the study drug is expected to have a teratogenic risk
   • Agree to use two effective contraception

10. Male subjects must

    • Agree to use condoms
    • Agree not to donate semen

11. All subjects must

    • Agree to abstain from donating blood
    • Agree not to share study drug with another person

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Use of any other experimental drug or therapy within 28 days of baseline.
5. Known hypersensitivity to thalidomide.
6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Any prior use of lenalidomide.
8. Concurrent use of other anti-cancer agents or treatments.
9. Known positive for HIV or infectious hepatitis, type A, B or C.