Revlimid in Transfusion Dependent Patients

The first Revlimid® study reported by List et al included all transfusion dependent MDS
patients, but given the early experience which showed a better response in del(5q) patients
and those with lower risk disease, more patients belonging to this category were entered on
the trial. The subsequent multi-center studies were focused entirely on the low/Int-1
patients who were transfusion dependent. In the present study, we would like to recapitulate
the initial study by only treating the transfusion dependent, low and intermediate-1 risk MDS
patients without deletion (5q). Since the predictive assay is most applicable for the
non-del(5q) patients, and to avoid confusion resulting from an admixture of patients with
del(5q) for whom the drug is already FDA approved, we have elected to restrict this clinical
trial to only the non-del(5q) patients.

In the present study, only the non-del(5q) transfusion dependent, low and intermediate-1 risk
MDS patients will be treated with single agent Revlimid®. All patients will have their
pre-therapy bone marrows studied by gene expression microarray, Luminex bead assay, and
real-time PCR.

Inclusion Criteria:

- Understand and voluntarily sign an informed consent form.

- Age ≥ 21 years at the time of signing the informed consent form.

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

- A confirmed diagnosis (using standard FAB criteria) of a myelodysplastic syndrome with
low/Int-1 risk and with a non-del(5q) karyotype must be established.

- Patients must have transfusion dependence (at least 2 units within 8 weeks prior to
starting therapy).

- All transfusion dependent non-del(5q) low/Int-1 risk patients will be eligible for
treatment with Revlimid®

- Newly diagnosed as well as previously treated patients will be eligible

- Patients with primary de novo or secondary MDS will be eligible

- All previous cancer therapy, including radiation, hormonal therapy and surgery, must
have been discontinued at least 4 weeks prior to treatment in this study.

- ECOG performance status of 0-2 at study entry (see Appendix II).

- Laboratory test results within these ranges:

- Absolute neutrophil count > 250/uL

- Platelet count > 30,000/uL

- Serum creatinine ≤ 2.0 mg/dL

- Total bilirubin ≤ 1.5 mg/dL

- AST (SGOT) and ALT (SGPT) ≤ 3 x ULN

- BUN ≤ 2 x ULN

- Disease free of prior malignancies for ≥ 2 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
or breast.

- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.

- Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
and again within 24 hours of prescribing lenalidomide (prescriptions must be filled
within 7 days) and must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control, one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men
must agree to use a latex condom during sexual contact with a FCBP even if they have
had a successful vasectomy.

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.

- Any clinically significant cardiac disease, including congestive heart failure

- Liver function studies including SGOT/SGPT > 3 x ULN

- Clinically significant renal disease.

- Any previous chemotherapy, hematopoietic growth factors, erythropoietin, or cytokines
within 4 weeks of starting treatment. Note: prior therapy with G-CSF within 4 weeks is
allowed.

- Use of any other experimental drug or therapy within 28 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. (Patients with prior therapy with thalidomide will be
eligible as long as at least 4 weeks have elapsed between end of the drug and accrual
on the present trial)

- Concurrent use of other anti-cancer agents or treatments.

- Known positive for HIV or infectious hepatitis, type B or C.

- Life expectancy < 3 months