Trial of High Dose Lenalidomide in Patients With MDS and AML With Trilineage Dysplasia

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.