Lack of efficacy

This is a phase II study of lenalidomide in patients with myelodysplastic syndrome (MDS) and with acute myeloid leukemia (AML) with trilineage dysplasia. Patients will receive two cycles of lenalidomide. Patients who respond may given additional cycles of lenalidomide until disease progression.

This is a single center open label phase II study of lenalidomide in IPSS Int-1 with increased blasts or hematologic needs with 5q31.1 deletions who have failed to respond to standard dose lenalidomide., IPSS Int-1 with increased blasts or hematologic needs without 5q31.1 deletions, and Int-2 and high risk myelodysplastic syndrome (MDS) patients with or without 5q31.1 deletions, regardless of whether they have received lenalidomide previously or not. Patients will receive two cycles of 15 mg daily lenalidomide (later amended to 50 mg daily lenalidomide) given on days 1-28 out of a 42 day cycle. Within each of the two cycles of lenalidomide, patients will be given up to three weeks with no drug treatment to recover. Patients who fail to respond after two cycles of treatment may receive two additional cycles if stable. Patients who develop clinical response may continue to receive drug until disease progression.

Inclusion Criteria:

• Age greater than 18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• MDS or MDS/AML
• Patients must not have received any other treatment for their disease, including hematopoietic growth factors, within three weeks of beginning the trial
• ECOG performance status of 0, 1, or 2 at study entry
• All study participants must be registered into the mandatory REMS® program, and be willing and able to comply with the requirements of RevAssist®.
• Patients must have no clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
• Subjects must agree to use appropriate contraception.

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
• 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.
• Use of any other experimental drug or therapy within 21 days of baseline.
• Known hypersensitivity to thalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Any prior use of lenalidomide except for MDS patients with del 5q31.1 abnormalities..
• Concurrent use of other anti-cancer agents or treatments.
• Patients may not have received prior AML induction chemotherapy or stem cell transplant. However, patients with secondary MDS who have received a stem cell transplant for other indications (eg lymphoma, multiple myeloma) will be eligible.

Up to 8 months

Due to significant cytopenias in all participants at presentation and throughout the trial, hematologic toxicity was only reported where bone marrow aplasia lasted for >3 weeks from last dose of lenalidomide with a bone marrow cellularity of <5% without evidence of leukemia. Adverse events were collected weekly throughout the trial.